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PRAGUE-17: LAA closure holds up against DOACs out to 4 years
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.
At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).
The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).
Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.
The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.
The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).
The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.
Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.
During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.
Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”
He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.
In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.
“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.
NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”
Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.
“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.
The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.
“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”
The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM TCT 2021
Direct comparison shows differing strengths for left atrial closure devices
On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.
But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.
At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.
Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
First randomized comparison with Watchman FLX
“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.
After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.
The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).
Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
Peridevice leaks twofold greater with Watchman
Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).
Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.
The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
Amulet IDE trial generates similar data
The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.
The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.
As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).
“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.
The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.
Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.
Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.
On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.
But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.
At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.
Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
First randomized comparison with Watchman FLX
“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.
After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.
The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).
Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
Peridevice leaks twofold greater with Watchman
Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).
Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.
The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
Amulet IDE trial generates similar data
The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.
The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.
As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).
“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.
The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.
Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.
Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.
On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.
But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.
At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.
Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
First randomized comparison with Watchman FLX
“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.
After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.
The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).
Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
Peridevice leaks twofold greater with Watchman
Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).
Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.
The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
Amulet IDE trial generates similar data
The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.
The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.
As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).
“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.
The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.
Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.
Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.
FROM TCT 2021
Fully endovascular mitral valve replacement a limited success in feasibility study
It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.
But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.
Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.
The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.
Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.
If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.
Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.
All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.
“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.
Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.
“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.
“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.
A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.
The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.
“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.
“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”
Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”
For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.
“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.
“The main question that the Intrepid early feasibility data raise is whether transfemoral, trans-septal TMVR will evolve to become the preferred strategy over transapical TMVR,” as occurred with transcatheter aortic-valve replacement (TAVR), the editorial states. “The answer is likely yes, but a few matters specific to trans-septal route will need be addressed first.”
Among those matters: The 35 F catheter leaves behind a considerable atrial septal defect (ASD). At operator discretion in this series, 11 patients received an ASD closure device.
None of the remaining four patients “developed significant heart failure or right ventricular dysfunction,” Dr. Zahr observed. “So, it seems like those patients who had their ASD left open tolerated it fairly well, at least until 30 days.”
But “we still need to learn what to do with those ASDs,” he said. “What is an acceptable residual shunt and what is an acceptable ASD size is to be determined.”
In general, the editorial notes, “the TMVR population has a high prevalence of cardiomyopathy, and a large residual iatrogenic ASD may lead to worsening volume overload and heart failure decompensation in some patients.”
Insertion of a closure device has its own issues, it continues. “Closure of the ASD might impede future access to the left atrium, which could impact life-long management of this high-risk population. A large septal occluder may hinder potentially needed procedures such as paravalvular leak closure, left atrial appendage closure, or pulmonary vein isolation.”
Patients like those in the current series, Dr. Kodali observed, will face “a lifetime of management challenges, and you want to make sure you don’t take away other options.”
The study was funded by Medtronic. Dr. Zahr reported institutional grant support from Edwards Lifesciences and Medtronic. Dr. Kodali disclosed consultant fees from Admedus and Dura Biotech; equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve, Supira, Admedus, TriFlo, and Anona; and institutional grant support from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. The editorial writers have disclosed no relevant financial relationships. Dr. Tayal disclosed consultant fees or honoraria from or serving on a speakers bureau for Abiomed, Edwards Lifesciences, Abbott Vascular, and Shockwave Medical.
A version of this article first appeared on Medscape.com.
It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.
But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.
Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.
The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.
Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.
If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.
Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.
All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.
“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.
Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.
“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.
“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.
A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.
The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.
“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.
“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”
Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”
For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.
“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.
“The main question that the Intrepid early feasibility data raise is whether transfemoral, trans-septal TMVR will evolve to become the preferred strategy over transapical TMVR,” as occurred with transcatheter aortic-valve replacement (TAVR), the editorial states. “The answer is likely yes, but a few matters specific to trans-septal route will need be addressed first.”
Among those matters: The 35 F catheter leaves behind a considerable atrial septal defect (ASD). At operator discretion in this series, 11 patients received an ASD closure device.
None of the remaining four patients “developed significant heart failure or right ventricular dysfunction,” Dr. Zahr observed. “So, it seems like those patients who had their ASD left open tolerated it fairly well, at least until 30 days.”
But “we still need to learn what to do with those ASDs,” he said. “What is an acceptable residual shunt and what is an acceptable ASD size is to be determined.”
In general, the editorial notes, “the TMVR population has a high prevalence of cardiomyopathy, and a large residual iatrogenic ASD may lead to worsening volume overload and heart failure decompensation in some patients.”
Insertion of a closure device has its own issues, it continues. “Closure of the ASD might impede future access to the left atrium, which could impact life-long management of this high-risk population. A large septal occluder may hinder potentially needed procedures such as paravalvular leak closure, left atrial appendage closure, or pulmonary vein isolation.”
Patients like those in the current series, Dr. Kodali observed, will face “a lifetime of management challenges, and you want to make sure you don’t take away other options.”
The study was funded by Medtronic. Dr. Zahr reported institutional grant support from Edwards Lifesciences and Medtronic. Dr. Kodali disclosed consultant fees from Admedus and Dura Biotech; equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve, Supira, Admedus, TriFlo, and Anona; and institutional grant support from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. The editorial writers have disclosed no relevant financial relationships. Dr. Tayal disclosed consultant fees or honoraria from or serving on a speakers bureau for Abiomed, Edwards Lifesciences, Abbott Vascular, and Shockwave Medical.
A version of this article first appeared on Medscape.com.
It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.
But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.
Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.
The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.
Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.
If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.
Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.
All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.
“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.
Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.
“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.
“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.
A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.
The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.
“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.
“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”
Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”
For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.
“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.
“The main question that the Intrepid early feasibility data raise is whether transfemoral, trans-septal TMVR will evolve to become the preferred strategy over transapical TMVR,” as occurred with transcatheter aortic-valve replacement (TAVR), the editorial states. “The answer is likely yes, but a few matters specific to trans-septal route will need be addressed first.”
Among those matters: The 35 F catheter leaves behind a considerable atrial septal defect (ASD). At operator discretion in this series, 11 patients received an ASD closure device.
None of the remaining four patients “developed significant heart failure or right ventricular dysfunction,” Dr. Zahr observed. “So, it seems like those patients who had their ASD left open tolerated it fairly well, at least until 30 days.”
But “we still need to learn what to do with those ASDs,” he said. “What is an acceptable residual shunt and what is an acceptable ASD size is to be determined.”
In general, the editorial notes, “the TMVR population has a high prevalence of cardiomyopathy, and a large residual iatrogenic ASD may lead to worsening volume overload and heart failure decompensation in some patients.”
Insertion of a closure device has its own issues, it continues. “Closure of the ASD might impede future access to the left atrium, which could impact life-long management of this high-risk population. A large septal occluder may hinder potentially needed procedures such as paravalvular leak closure, left atrial appendage closure, or pulmonary vein isolation.”
Patients like those in the current series, Dr. Kodali observed, will face “a lifetime of management challenges, and you want to make sure you don’t take away other options.”
The study was funded by Medtronic. Dr. Zahr reported institutional grant support from Edwards Lifesciences and Medtronic. Dr. Kodali disclosed consultant fees from Admedus and Dura Biotech; equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve, Supira, Admedus, TriFlo, and Anona; and institutional grant support from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. The editorial writers have disclosed no relevant financial relationships. Dr. Tayal disclosed consultant fees or honoraria from or serving on a speakers bureau for Abiomed, Edwards Lifesciences, Abbott Vascular, and Shockwave Medical.
A version of this article first appeared on Medscape.com.
At 5 years, iFR found as effective and safe as FFR for guiding PCI intervention
The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.
“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.
When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.
These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).
In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
No differences seen across outcomes
When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).
Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.
At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.
“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.
While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
Patient discomfort is greater with FFR
Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.
Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.
Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.
The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.
Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.
For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.
However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.
Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.
The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.
“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.
When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.
These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).
In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
No differences seen across outcomes
When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).
Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.
At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.
“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.
While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
Patient discomfort is greater with FFR
Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.
Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.
Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.
The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.
Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.
For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.
However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.
Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.
The rate of major adverse cardiac events (MACE) over 5 years is similar whether revascularization is guided by instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR), according to long-term results of the iFR-SWEDEHEART study.
“The results are about the same as reported at 12 months. There were no significant differences in any outcome we evaluated,” according to Matthias Götberg, MD, PhD.
When the initial results of the noninferiority iFR-SWEDEHEART trial were published after 1 year of follow-up, the primary MACE endpoint of death from any-cause nonfatal myocardial infarction, or unplanned revascularization, was met by 6.7% and 6.1% of those randomized to iFR or FFR, respectively.
These outcomes were not significantly different and placed iFR well within the predefined boundaries of noninferiority (P = .007).
In this new and final follow-up of iFR-SWEDEHEART, which evaluated the same 2,019 patients who were alive at 1 year (none were lost to follow-up), the MACE endpoint was met by 21.5% and 19.9% of those managed with iFR and FFR, respectively. The hazard ratio (1.09) had a wide 95% confidence interval (0.90-1.31) that did not approach statistical significance.
No differences seen across outcomes
When broken down into the MACE components, there were no differences between iFR and FFR, respectively, for all-cause death (9.4% vs. 7.9%), MI (5.8% vs. 5.7%) or unplanned revascularization (11.6% vs. 11.3%).
Across predefined subgroups, such as those defined by age, gender, stable versus unstable angina, and presence of risk factors such as diabetes, hypertension, hyperlipidemia, and smoking, there were also no significant differences in outcome.
At the time iFR-SWEDEHART was initiated, FFR had already been accepted as more effective than angiographic assessment to identify lesion ischemia and the need for percutaneous intervention (PCI). The iFR-SWEDEHEART trial tested iFR, a relatively new technology at the time, as a noninferior alternative. Unlike FFR, which requires adenosine to dilate the vessel, adding cost and patient discomfort, iFR measures the resting pressure gradient across the coronary lesion, and it is generally easier to perform.
“The advantage of iFR is that it provides an instantaneous lesion assessment without the need for adenosine,” Dr. Götberg explained in presenting the results at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
When the procedural results were compared in the published study at 1 year, it was noted that the mean number of lesions evaluated per patient was higher (1.55 vs. 1.43; P = .002), but the proportion of lesions found functionally significant was lower (29.2% vs. 36.8%; P < .0001) among those randomized to iFR than in the FFR group.
While most other procedural characteristics, such as PCI access route, fluoroscopy time, and contrast use did not differ significantly, fewer stents were placed in patients managed with iFR (1.58 vs. 1.73; P = .048), and a reduction in the average procedural time of a few minutes approached significance (P = .09).
Patient discomfort is greater with FFR
Patient discomfort measured during the procedure did differ, according to Dr. Götberg, an interventional cardiologist at Skåne University Hospital, Lund, Sweden.
Only about 30% in the FFR group reported no discomfort. Most of the others reported mild or moderate discomfort, but nearly 10% characterized the discomfort as severe. In the iFR group, more than 95% reported no discomfort. All of the remaining patients reported discomfort level as mild.
Because differences in MACE would be most likely to occur in the first year after revascularization, the similarity of the 1- and 5-year results were expected, according to Dr. Götberg. However, a 5-year follow-up was considered prudent given the relatively limited experience with iFR when the study was designed. This technique is now well established and widely used.
The study supports the premise that quicker and easier-to-obtain results with iFR are obtained without sacrificing greater relative risk of failing to identify a vulnerable lesion, according to Dr. Götberg.
Nevertheless, iFR and FFR “are not an exact match,” according to Jennifer A. Rymer, MD, an interventional cardiologist and assistant professor of medicine at Duke University, Durham, N.C. Although she called this trial an “excellent” demonstration of comparable utility in distinguishing lesions that do not require intervention from those that do, she implied that some clinicians might still prefer FFR for other reasons.
For example, FFR provides information about coronary flow reserve and microvascular resistance that are relevant to the underlying pathophysiology in a diseased vessel, according to Shmuel Banai, MD, head of interventional cardiology, Tel Aviv Medical Center. Recognizing that this information is not as readily generated by iFR, he is among those who plan to continue to use FFR despite these results.
However, for those who are now routinely performing iFR for the purposes of guiding revascularization, “these data are reassuring,” said David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta. The 5-year data essentially eliminate the likelihood that iFR relative to FFR increases the risk of missing functionally significant lesions for revascularization procedures.
Dr. Götberg reports financial relationships with Abbott, Boston Scientific, Medtronic, and Phillips Healthcare. Dr. Rymer reports no potential financial conflicts of interest. Dr. Banai has a financial relationship with Neovasc. Dr. Kandzari reports financial relationships with Ablative Solutions and Medtronic.
FROM TCT 2021
Short DAPT course beneficial after PCI in ‘bi-risk’ patients
Ischemic events not increased
Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.
In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.
MASTER DAPT main results published
The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.
In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.
[embed:render:related:node:244920]
Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).
When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.
Recent MI vs. no MI
In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.
In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).
For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.
“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
No difference in NACE components
In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.
There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).
As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).
In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.
According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.
“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.
Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.
Ischemic events not increased
Ischemic events not increased
Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.
In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.
MASTER DAPT main results published
The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.
In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.
[embed:render:related:node:244920]
Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).
When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.
Recent MI vs. no MI
In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.
In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).
For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.
“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
No difference in NACE components
In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.
There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).
As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).
In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.
According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.
“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.
Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.
Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.
In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.
“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.
MASTER DAPT main results published
The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.
In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.
[embed:render:related:node:244920]
Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).
When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.
Recent MI vs. no MI
In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.
In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).
For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.
“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
No difference in NACE components
In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.
There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).
As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).
In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.
According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.
“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.
Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.
FROM TCT 2021
FAVOR III China: QFR-guided PCI shows advantage over angiography
Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.
PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.
“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.
The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.
Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.
QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.
FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).
In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.
PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.
The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).
The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.
The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).
The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).
“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.
“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.
In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”
They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.
They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.
Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”
Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”
Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.
The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.
A version of this article first appeared on Medscape.com.
Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.
PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.
“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.
The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.
Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.
QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.
FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).
In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.
PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.
The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).
The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.
The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).
The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).
“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.
“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.
In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”
They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.
They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.
Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”
Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”
Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.
The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.
A version of this article first appeared on Medscape.com.
Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.
PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.
“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.
The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.
Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.
QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.
FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).
In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.
PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.
The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).
The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.
The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).
The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).
“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.
“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.
In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”
They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.
They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.
Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”
Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”
Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.
The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.
A version of this article first appeared on Medscape.com.
FFR-guided PCI falls short vs. surgery in multivessel disease: FAME 3
Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.
Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.
Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.
The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.
One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.
“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”
Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
[embed:render:related:node:155331]
He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.
“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.
“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.
A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.
Not all that surprising
“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.
“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.
Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.
In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”
Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”
Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”
The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.
The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.
FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
Did the primary endpoint favor CABG?
At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”
It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.
Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).
Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.
Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”
And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.
“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”
FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.
A version of this article first appeared on Medscape.com.
Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.
Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.
Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.
The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.
One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.
“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”
Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
[embed:render:related:node:155331]
He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.
“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.
“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.
A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.
Not all that surprising
“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.
“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.
Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.
In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”
Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”
Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”
The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.
The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.
FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
Did the primary endpoint favor CABG?
At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”
It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.
Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).
Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.
Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”
And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.
“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”
FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.
A version of this article first appeared on Medscape.com.
Coronary stenting guided by fractional flow reserve (FFR) readings, considered to reflect the targeted lesion’s functional impact, was no match for coronary bypass surgery (CABG) in patients with multivessel disease (MVD) in a major international randomized trial.
Indeed, FFR-guided percutaneous coronary intervention (PCI) using one of the latest drug-eluting stents (DES) seemed to perform poorly in the trial, compared with surgery, apparently upping the risk for clinical events by 50% over 1 year.
Designed statistically for noninferiority, the third Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 3) trial, with 1,500 randomized patients, showed that FFR-guided PCI was “not noninferior” to CABG. Of those randomized to PCI, 10.6% met the 1-year primary endpoint of major adverse cardiac or cerebrovascular events (MACCE), compared with only 6.9% of patients assigned to CABG.
The trial enrolled only patients with three-vessel coronary disease with no left-main coronary artery involvement, who were declared by their institution’s multidisciplinary heart team to be appropriate for either form of revascularization.
One of the roles of FFR for PCI guidance is to identify significant lesions “that are underrecognized by the angiogram,” which is less likely to happen in patients with very complex coronary anatomy, study chair William F. Fearon, MD, Stanford (Calif.) University, said in an interview.
“That’s what we saw in a subgroup analysis based on SYNTAX score,” an index of lesion complexity. “In patients with very high SYNTAX scores, CABG outperformed FFR-guided PCI. But if you look at patients with low SYNTAX scores, actually, FFR-guided PCI outperformed CABG for 1-year MACCE.”
Dr. Fearon is lead author on the study’s Nov. 4, 2021, publication in the New England Journal of Medicine, its release timed to coincide with his presentation of the trial at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
[embed:render:related:node:155331]
He noted that FAME-3 “wasn’t designed or powered to test for superiority,” so its results do not imply CABG is superior to FFR-PCI in patients with MVD, and remains “inconclusive” on that question.
“I think what this study does is provide both the physician and patients more contemporary data and information on options and expected outcomes in multivessel disease. So if you are a patient who has less complex disease, I think you can feel comfortable that you will get an equivalent result with FFR-guided PCI.” But, at least based on FAME-3, Dr. Fearon said, CABG provides better outcomes in patients with more complex disease.
“I think there are still patients that look at trade-offs. Some patients will accept a higher event rate in order to avoid a long recovery, and vice versa.” So the trial may allow patients and physicians to make more informed decisions, he said.
A main message of FAME-3 “is that we’re getting very good results with three-vessel PCI, but better results with surgery,” Ran Kornowski, MD, Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, said as a discussant following Dr. Fearon’s presentation of the trial. The subanalysis by SYNTAX score, he agreed, probably could be used as part of shared decision-making with patients.
Not all that surprising
“It’s a well-designed study, with a lot of patients,” said surgeon Frank W. Sellke, MD, of Rhode Island Hospital, Miriam Hospital, and Brown University, all in Providence.
“I don’t think it’s all that surprising,” he said in an interview. “It’s very consistent with what other studies have shown, that for three-vessel disease, surgery tends to have the edge,” even when pitted against FFR-guided PCI.
Indeed, pressure-wire FFR-PCI has a spotty history, even as an alternative to standard angiography-based PCI. For example, it has performed well in registry and other cohort studies but showed no advantage in the all-comers RIPCORD-2 trial or in the setting of complete revascularization PCI for acute MI in FLOWER-MI. And it emitted an increased-mortality signal in the prematurely halted FUTURE trial.
In FAME-3, “the 1-year follow-up was the best chance for FFR-PCI to be noninferior to CABG. The CABG advantage is only going to get better with time if prior experience and pathobiology is true,” Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
Overall, “the quality and quantity of evidence is insufficient to support FFR-guided PCI” in patients with complex coronary artery disease (CAD), he said. “I would also argue that the evidence for FFR-guided PCI for simple CAD is also not high quality.”
Dr. Kaul also blasted the claim that FFR-PCI was seen to perform better against CABG in patients with low SYNTAX scores. “In general, one cannot use a positive subgroup in a null or negative trial, as is the case with FAME-3, to ‘rescue’ the treatment intervention.” Such a positive subgroup finding, he said, “would at best be deemed hypothesis-generating and not hypothesis validating.”
Dr. Fearon agreed that the subgroup analysis by SYNTAX score, though prespecified, was only hypothesis generating. “But I think that other studies have shown the same thing – that in less complex disease, the two strategies appear to perform in a similar fashion.”
The FAME-3 trial’s 1,500 patients were randomly assigned at 48 centers to undergo standard CABG or FFR-guided PCI with Resolute Integrity (Medtronic) zotarolimus-eluting DES. Lesions with a pressure-wire FFR of 0.80 or less were stented and those with higher FFR readings were deferred.
The 1-year hazard ratio for the primary endpoint—a composite of death from any cause, MI, stroke, or repeat revascularization – was 1.5 (95% confidence interval, 1.1-2.2) with a noninferiority P value of .35 for the comparison of FFR-PCI versus CABG.
FFR-guided PCI fared significantly better than CABG for some safety endpoints, including major bleeding (1.6% vs 3.8%, P < .01), arrhythmia including atrial fibrillation (2.4% vs. 14.1%, P < .001), acute kidney injury (0.1% vs 0.9%, P < .04), and 30-day rehospitalization (5.5% vs 10.2%, P < .001).
Did the primary endpoint favor CABG?
At a media briefing prior to Dr. Fearon’s TCT 2021 presentation of the trail, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, proposed that the inclusion of repeat revascularization in the trial’s composite primary endpoint tilted the outcome in favor of CABG. “To me, the FAME-3 results are predictable because repeat revascularization is in the equation.”
It’s well recognized that the endpoint is less likely after CABG than PCI. The latter treats focal lesions that are a limited part of a coronary artery in which CAD is still likely progressing. CABG, on the other hand, can bypass longer segments of diseased artery.
Indeed, as Dr. Fearon reported, the rates of death, MI, or stroke excluding repeat revascularization were 7.3% with FFR-PCI and 5.2% for CABG, for an HR of 1.4 (95% CI, 0.9-2.1).
Dr. Mehran also proposed that intravascular-ultrasound (IVUS) guidance, had it been part of the trial, could potentially have boosted the performance of FFR-PCI.
Repeat revascularization, Dr. Kaul agreed, “should not have been included” in the trial’s primary endpoint. It had been added “to amplify events and to minimize sample size. Not including revascularization would render the sample size prohibitive. There is always give and take in designing clinical trials.”
And he agreed that “IVUS-based PCI optimization would have further improved PCI outcomes.” However, “IVUS plus FFR adds to the procedural burden and limited resources available.” Dr. Fearon said when interviewed that the trial’s definition of procedural MI, a component of the primary endpoint, might potentially be seen as controversial. Procedural MIs in both the PCI and CABG groups were required to meet the standards of CABG-related type-5 MI according to the third and fourth Universal Definitions. The had also had to be accompanied by “a significant finding like new Q waves or a new wall-motion abnormality on echocardiography,” he said.
“That’s fairly strict. Because of that, we had a low rate of periprocedural MI and it was similar between the two groups, around 1.5% in both arms.”
FAME-3 was funded by Medtronic and Abbott Vascular. Dr. Kaul disclosed no relevant financial relationships. Dr. Kornowsky receives royalties from or holds intellectual property rights with CathWorks. Dr. Mehran disclosed financial ties to numerous pharmaceutical and device companies, and that she, her spouse, or her institution hold equity in Elixir Medical, Applied Therapeutics, and ControlRad.
A version of this article first appeared on Medscape.com.
SUGAR trial finds superior stent for those with diabetes and CAD
Superiority shown on TLF endpoint
Designed to show noninferiority for treatment of coronary artery disease (CAD) in patients with diabetes, a head-to-head comparison of contemporary stents ended up showing that one was superior to the for the primary endpoint of target lesion failure (TLF).
In the superiority analysis, the 35% relative reduction in the risk of TLF at 1 year for the Cre8 EVO (Alvimedica) stent relative to the Resolute Onyx (Medtronic) device reached significance, according to Rafael Romaguera, MD, PhD, an interventional cardiologist at the Bellvitge University Hospital, Barcelona.
At 1 year, the rates of TLF were 7.2% and 10.5% for the Cre8 EVO and Resolute Onyx stents, respectively. On the basis of noninferiority, the 3.73% reduction in TLF at 1 year among those receiving the Cre8 EVO device provided a highly significant confirmation of noninferiority (P < .001) and triggered the preplanned superiority analysis.
When the significant advantage on the TLF endpoint (P = .03) was broken down into its components, the Cre8 EVO stent was linked to numerically lower rates of cardiac death (2.1% vs. 2.7%), target vessel MI (5.3% vs. 7.2%), and target lesion revascularization (2.4% vs. 3.9%), according to the SUGAR (Second-Generation Drug-Eluting Stents in Diabetes) trial results presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
In a previous study comparing these devices, called the ReCre8 trial, the rates of TLF in an all-comer CAD population were similar at 1 year. When an updated 3-year analysis was presented earlier in 2021 at the Cardiovascular Research Technologies meeting, they remained similar.
Diabetes-centered trial was unmet need
The rationale for conducting a new trial limited to patients with diabetes was based on the greater risk in this population, according to Dr. Romaguera. He cited data that indicate the risk of major adverse cardiac events are about two times higher 2 years after stent implantation in patients with diabetes relative to those without, even when contemporary drug-eluting stents are used.
Both the Cre8 EVO and Resolute Onyx stent are drug eluting and employ contemporary architecture that provides the basis for marketing claims that they are suitable for complex patients; but they have differences.
“There are three features that I think differentiate the Cre8 EVO stent,” Dr. Romaguera reported at the meeting, sponsored by the Cardiovascular Research Foundation.
One is the absence of polymer, which contrasts with the permanent polymer of the Resolute device. This feature affects the dissolution of the anti-inflammatory drug and might be one explanation for the greater protection from ischemic events, according to Dr. Romaguera.
Another is the thickness of the struts, which range from 70 to 80 mm for the Cre8 EVO device and from 92 to 102 mm for the Resolute Onyx device. In experimental studies, strut thickness has been associated with greater risk of thrombus formation, although it is unclear if this modest difference is clinically significant.
Also important, the Cre8 EVO device employs sirolimus for an anti-inflammatory effect, while the Resolute Onyx elutes zotarolimus. Again, experimental evidence suggests a greater anti-inflammatory effect reduces the need for dual-antiplatelet therapy (DAPT); that might offer a relative advantage in patients with an elevated risk of bleeding.
It is not clear whether all of these features contribute to the better results observed in this trial in diabetes patients, but Dr. Romaguera indicated that the lower risk of TLF with Cre8 EVO is not just statistically significant but also clinically meaningful.
In SUGAR, which included 23 centers in Spain, 1,175 patients with confirmed diabetes scheduled for percutaneous intervention (PCI) were randomized to one of the two stents. The study was purposely designed with very few exclusion criteria.
SUGAR trial employed all-comer design
“This was an all-comer design and there was no limitation in regard to clinical presentation, complexity, number of lesions, or other disease features,” said Dr. Romaguera. The major exclusions were a life expectancy of less than 2 years and a contraindication to taking DAPT for at least 1 month,
The patients were almost equally divided between those who had a non–ST-segment elevation MI) and those with chronic coronary artery disease, but patients with a STEMI, representing about 12% of the population, were included. Almost all of the patients (about 95%) had type 2 diabetes; nearly one-third were on insulin at the time of randomization.
According to Dr. Romaguera, “SUGAR is the first powered trial to compare new-generation drug-eluting stents in patients with diabetes,” and he emphasized the all-comer design in supporting its clinical relevance.
Several of those participating in discussion of the trial during the late-breaker session agreed. Although the moderator, Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai, New York, expressed surprise that the trial “actually demonstrated superiority” given the difficulty of showing a difference between modern stents, he called the findings “remarkable.”
Others seemed to suggest that it would alter their practice.
“This study is sweet like sugar for us, because now we have a stent that is dedicated and fitted for the diabetic population,” said Gennaro Sardella, MD, of Sapienza University of Rome.
For Marc Etienne Jolicoeur, MD, an interventional cardiologist associated with Duke University, Durham, N.C., one of the impressive findings was the early separation of the curves in favor of Cre8 EVO. Calling SUGAR a “fantastic trial,” he indicated that the progressive advantage over time reinforced his impression that the difference is real.
However, David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta, was more circumspect. He did not express any criticisms of the trial, but he called for “a larger evidence base” before declaring the Cre8 EVO device a standard of care for patients with diabetes undergoing PCI.
The SUGAR results were published in the European Heart Journal at the time of presentation at the meeting.
The trial was funded by the Spanish Society of Cardiology. Dr. Romaguera reported financial relationships with Biotronik and Boston Scientific. Dr. Stone, has financial relationships with more than 10 pharmaceutical companies, including those developing devices used in PCI. Dr. Sardella and Dr. Jolicoeur reported no financial relationships relevant to this topic. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
Superiority shown on TLF endpoint
Superiority shown on TLF endpoint
Designed to show noninferiority for treatment of coronary artery disease (CAD) in patients with diabetes, a head-to-head comparison of contemporary stents ended up showing that one was superior to the for the primary endpoint of target lesion failure (TLF).
In the superiority analysis, the 35% relative reduction in the risk of TLF at 1 year for the Cre8 EVO (Alvimedica) stent relative to the Resolute Onyx (Medtronic) device reached significance, according to Rafael Romaguera, MD, PhD, an interventional cardiologist at the Bellvitge University Hospital, Barcelona.
At 1 year, the rates of TLF were 7.2% and 10.5% for the Cre8 EVO and Resolute Onyx stents, respectively. On the basis of noninferiority, the 3.73% reduction in TLF at 1 year among those receiving the Cre8 EVO device provided a highly significant confirmation of noninferiority (P < .001) and triggered the preplanned superiority analysis.
When the significant advantage on the TLF endpoint (P = .03) was broken down into its components, the Cre8 EVO stent was linked to numerically lower rates of cardiac death (2.1% vs. 2.7%), target vessel MI (5.3% vs. 7.2%), and target lesion revascularization (2.4% vs. 3.9%), according to the SUGAR (Second-Generation Drug-Eluting Stents in Diabetes) trial results presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
In a previous study comparing these devices, called the ReCre8 trial, the rates of TLF in an all-comer CAD population were similar at 1 year. When an updated 3-year analysis was presented earlier in 2021 at the Cardiovascular Research Technologies meeting, they remained similar.
Diabetes-centered trial was unmet need
The rationale for conducting a new trial limited to patients with diabetes was based on the greater risk in this population, according to Dr. Romaguera. He cited data that indicate the risk of major adverse cardiac events are about two times higher 2 years after stent implantation in patients with diabetes relative to those without, even when contemporary drug-eluting stents are used.
Both the Cre8 EVO and Resolute Onyx stent are drug eluting and employ contemporary architecture that provides the basis for marketing claims that they are suitable for complex patients; but they have differences.
“There are three features that I think differentiate the Cre8 EVO stent,” Dr. Romaguera reported at the meeting, sponsored by the Cardiovascular Research Foundation.
One is the absence of polymer, which contrasts with the permanent polymer of the Resolute device. This feature affects the dissolution of the anti-inflammatory drug and might be one explanation for the greater protection from ischemic events, according to Dr. Romaguera.
Another is the thickness of the struts, which range from 70 to 80 mm for the Cre8 EVO device and from 92 to 102 mm for the Resolute Onyx device. In experimental studies, strut thickness has been associated with greater risk of thrombus formation, although it is unclear if this modest difference is clinically significant.
Also important, the Cre8 EVO device employs sirolimus for an anti-inflammatory effect, while the Resolute Onyx elutes zotarolimus. Again, experimental evidence suggests a greater anti-inflammatory effect reduces the need for dual-antiplatelet therapy (DAPT); that might offer a relative advantage in patients with an elevated risk of bleeding.
It is not clear whether all of these features contribute to the better results observed in this trial in diabetes patients, but Dr. Romaguera indicated that the lower risk of TLF with Cre8 EVO is not just statistically significant but also clinically meaningful.
In SUGAR, which included 23 centers in Spain, 1,175 patients with confirmed diabetes scheduled for percutaneous intervention (PCI) were randomized to one of the two stents. The study was purposely designed with very few exclusion criteria.
SUGAR trial employed all-comer design
“This was an all-comer design and there was no limitation in regard to clinical presentation, complexity, number of lesions, or other disease features,” said Dr. Romaguera. The major exclusions were a life expectancy of less than 2 years and a contraindication to taking DAPT for at least 1 month,
The patients were almost equally divided between those who had a non–ST-segment elevation MI) and those with chronic coronary artery disease, but patients with a STEMI, representing about 12% of the population, were included. Almost all of the patients (about 95%) had type 2 diabetes; nearly one-third were on insulin at the time of randomization.
According to Dr. Romaguera, “SUGAR is the first powered trial to compare new-generation drug-eluting stents in patients with diabetes,” and he emphasized the all-comer design in supporting its clinical relevance.
Several of those participating in discussion of the trial during the late-breaker session agreed. Although the moderator, Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai, New York, expressed surprise that the trial “actually demonstrated superiority” given the difficulty of showing a difference between modern stents, he called the findings “remarkable.”
Others seemed to suggest that it would alter their practice.
“This study is sweet like sugar for us, because now we have a stent that is dedicated and fitted for the diabetic population,” said Gennaro Sardella, MD, of Sapienza University of Rome.
For Marc Etienne Jolicoeur, MD, an interventional cardiologist associated with Duke University, Durham, N.C., one of the impressive findings was the early separation of the curves in favor of Cre8 EVO. Calling SUGAR a “fantastic trial,” he indicated that the progressive advantage over time reinforced his impression that the difference is real.
However, David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta, was more circumspect. He did not express any criticisms of the trial, but he called for “a larger evidence base” before declaring the Cre8 EVO device a standard of care for patients with diabetes undergoing PCI.
The SUGAR results were published in the European Heart Journal at the time of presentation at the meeting.
The trial was funded by the Spanish Society of Cardiology. Dr. Romaguera reported financial relationships with Biotronik and Boston Scientific. Dr. Stone, has financial relationships with more than 10 pharmaceutical companies, including those developing devices used in PCI. Dr. Sardella and Dr. Jolicoeur reported no financial relationships relevant to this topic. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
Designed to show noninferiority for treatment of coronary artery disease (CAD) in patients with diabetes, a head-to-head comparison of contemporary stents ended up showing that one was superior to the for the primary endpoint of target lesion failure (TLF).
In the superiority analysis, the 35% relative reduction in the risk of TLF at 1 year for the Cre8 EVO (Alvimedica) stent relative to the Resolute Onyx (Medtronic) device reached significance, according to Rafael Romaguera, MD, PhD, an interventional cardiologist at the Bellvitge University Hospital, Barcelona.
At 1 year, the rates of TLF were 7.2% and 10.5% for the Cre8 EVO and Resolute Onyx stents, respectively. On the basis of noninferiority, the 3.73% reduction in TLF at 1 year among those receiving the Cre8 EVO device provided a highly significant confirmation of noninferiority (P < .001) and triggered the preplanned superiority analysis.
When the significant advantage on the TLF endpoint (P = .03) was broken down into its components, the Cre8 EVO stent was linked to numerically lower rates of cardiac death (2.1% vs. 2.7%), target vessel MI (5.3% vs. 7.2%), and target lesion revascularization (2.4% vs. 3.9%), according to the SUGAR (Second-Generation Drug-Eluting Stents in Diabetes) trial results presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation.
In a previous study comparing these devices, called the ReCre8 trial, the rates of TLF in an all-comer CAD population were similar at 1 year. When an updated 3-year analysis was presented earlier in 2021 at the Cardiovascular Research Technologies meeting, they remained similar.
Diabetes-centered trial was unmet need
The rationale for conducting a new trial limited to patients with diabetes was based on the greater risk in this population, according to Dr. Romaguera. He cited data that indicate the risk of major adverse cardiac events are about two times higher 2 years after stent implantation in patients with diabetes relative to those without, even when contemporary drug-eluting stents are used.
Both the Cre8 EVO and Resolute Onyx stent are drug eluting and employ contemporary architecture that provides the basis for marketing claims that they are suitable for complex patients; but they have differences.
“There are three features that I think differentiate the Cre8 EVO stent,” Dr. Romaguera reported at the meeting, sponsored by the Cardiovascular Research Foundation.
One is the absence of polymer, which contrasts with the permanent polymer of the Resolute device. This feature affects the dissolution of the anti-inflammatory drug and might be one explanation for the greater protection from ischemic events, according to Dr. Romaguera.
Another is the thickness of the struts, which range from 70 to 80 mm for the Cre8 EVO device and from 92 to 102 mm for the Resolute Onyx device. In experimental studies, strut thickness has been associated with greater risk of thrombus formation, although it is unclear if this modest difference is clinically significant.
Also important, the Cre8 EVO device employs sirolimus for an anti-inflammatory effect, while the Resolute Onyx elutes zotarolimus. Again, experimental evidence suggests a greater anti-inflammatory effect reduces the need for dual-antiplatelet therapy (DAPT); that might offer a relative advantage in patients with an elevated risk of bleeding.
It is not clear whether all of these features contribute to the better results observed in this trial in diabetes patients, but Dr. Romaguera indicated that the lower risk of TLF with Cre8 EVO is not just statistically significant but also clinically meaningful.
In SUGAR, which included 23 centers in Spain, 1,175 patients with confirmed diabetes scheduled for percutaneous intervention (PCI) were randomized to one of the two stents. The study was purposely designed with very few exclusion criteria.
SUGAR trial employed all-comer design
“This was an all-comer design and there was no limitation in regard to clinical presentation, complexity, number of lesions, or other disease features,” said Dr. Romaguera. The major exclusions were a life expectancy of less than 2 years and a contraindication to taking DAPT for at least 1 month,
The patients were almost equally divided between those who had a non–ST-segment elevation MI) and those with chronic coronary artery disease, but patients with a STEMI, representing about 12% of the population, were included. Almost all of the patients (about 95%) had type 2 diabetes; nearly one-third were on insulin at the time of randomization.
According to Dr. Romaguera, “SUGAR is the first powered trial to compare new-generation drug-eluting stents in patients with diabetes,” and he emphasized the all-comer design in supporting its clinical relevance.
Several of those participating in discussion of the trial during the late-breaker session agreed. Although the moderator, Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai, New York, expressed surprise that the trial “actually demonstrated superiority” given the difficulty of showing a difference between modern stents, he called the findings “remarkable.”
Others seemed to suggest that it would alter their practice.
“This study is sweet like sugar for us, because now we have a stent that is dedicated and fitted for the diabetic population,” said Gennaro Sardella, MD, of Sapienza University of Rome.
For Marc Etienne Jolicoeur, MD, an interventional cardiologist associated with Duke University, Durham, N.C., one of the impressive findings was the early separation of the curves in favor of Cre8 EVO. Calling SUGAR a “fantastic trial,” he indicated that the progressive advantage over time reinforced his impression that the difference is real.
However, David Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta, was more circumspect. He did not express any criticisms of the trial, but he called for “a larger evidence base” before declaring the Cre8 EVO device a standard of care for patients with diabetes undergoing PCI.
The SUGAR results were published in the European Heart Journal at the time of presentation at the meeting.
The trial was funded by the Spanish Society of Cardiology. Dr. Romaguera reported financial relationships with Biotronik and Boston Scientific. Dr. Stone, has financial relationships with more than 10 pharmaceutical companies, including those developing devices used in PCI. Dr. Sardella and Dr. Jolicoeur reported no financial relationships relevant to this topic. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
FROM TCT 2021
Renal denervation remains only promising, per latest meta-analysis
Questions remain despite efficacy
According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.
Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.
For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.
Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
Office-based systolic reduction: 6 mm Hg
When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.
Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.
[embed:render:related:node:217924]
Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.
According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.
More than 20 meta-analyses published so far
By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.
Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.
The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.
Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.
“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
Individual study data also relevant
Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.
So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”
“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.
“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.
But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.
“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.
“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.
Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
Questions remain despite efficacy
Questions remain despite efficacy
According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.
Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.
For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.
Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
Office-based systolic reduction: 6 mm Hg
When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.
Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.
[embed:render:related:node:217924]
Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.
According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.
More than 20 meta-analyses published so far
By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.
Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.
The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.
Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.
“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
Individual study data also relevant
Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.
So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”
“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.
“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.
But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.
“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.
“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.
Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.
Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.
For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.
Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
Office-based systolic reduction: 6 mm Hg
When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.
Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.
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Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.
According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.
More than 20 meta-analyses published so far
By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.
Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.
The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.
Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.
“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
Individual study data also relevant
Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.
So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”
“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.
“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.
But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.
“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.
“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.
Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.
FROM TCT 2021
Real-world data favor invasive strategy for NSTEMI with CKD
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
