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Surgical left atrial appendage closure slashes stroke risk
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The composite rate of clinical stroke, TIA, or silent cerebral infarct in the years following open heart surgery was threefold higher in patients randomized to no prophylactic surgical closure of the left atrial appendage, compared with patients who got appendage closure during their surgery.
Data source: A randomized trial in which 141 patients undergoing first-time open heart surgery were assigned to prophylactic surgical closure of the left atrial appendage or not.
Disclosures: The study was conducted free of commercial support. The presenter reported having no financial conflicts of interest.
LDL levels below 10 mg/dL shown safe, effective
BARCELONA – The maxim that lower is better for LDL cholesterol continues to hold true, even at jaw-droppingly low levels of less than 10 mg/dL in a new analysis of data from the FOURIER trial.
The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial was the pivotal efficacy and safety study for the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor evolocumab (Repatha) and enrolled patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of at least 70 mg/dL (N Engl J Med. 2017 May 4;376[18]:1713-22).
After a median follow-up of 26 months, the incidence of the study’s primary endpoint (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) dropped by a statistically significant 15% in patients with an achieved LDL cholesterol of 20-49 mg/dL, compared with patients whose 4-week LDL cholesterol was at or above 100 mg/dL (primarily patients randomized to the study’s control arm), by 24% in all patients with LDL cholesterol less than 20 mg/dL, and by 31% in the 2% of patients whose LDL cholesterol levels fell below 10 mg/dL.
These strikingly improved event rates at the lowest levels of LDL cholesterol occurred with no signal of excess adverse events, Robert P. Giugliano, MD, said at the annual congress of the European Society of Cardiology.
In contrast, the 13% of patents whose achieved LDL cholesterol was 50-69 mg/dL had an event rate just 6% below the referent group of 100 mg/dL or more, a nonsignificant difference. Existing cholesterol management guidelines that set LDL cholesterol targets for secondary prevention have used a level below 70 mg/dL as the target, such as the European Society of Cardiology’s 2016 guidelines (Eur Heart J. 2016 Oct 14;37[39]:2999-3058).
“The data suggest that we should target considerably lower LDL cholesterol than is currently recommended for our patients with atherosclerotic cardiovascular disease,” said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Lowest is best with LDL. You don’t need a lot of LDL in the serum for normal human function,” he noted during the discussion of his report.
While FOURIER’s event curve continued to drop as LDL cholesterol fell below 10 mg/dL, the study’s wide-ranging safety assessment showed no signal of harm at the lowest levels. This “gives us some reassurance it’s safe,” he said in an interview. “We saw benefit that continued down to the lowest LDL levels, so it’s hard to pick a LDL target. I no longer feel comfortable treating my patients to just less than 70 mg/dL. I’m not sure what is the optimal LDL target, but I think it needs to be lower than that.”
To achieve such ultralow LDL levels, most patients need treatment with a PCSK9 inhibitor plus at least one and perhaps two additional cholesterol-lowering drugs, a statin and ezetimibe, he noted.
The FOURIER analyses Dr. Giugliano reported included data on the incidence during the study of 10 specific types of adverse events: noncardiovascular death, serious adverse events, adverse events leading to study discontinuation, and new onset of diabetes, cancer, cataract, neurocognitive deficit, significant liver enzyme increase, significant creatine kinase increase, and hemorrhagic stroke. The incidence of each of these was similar among the patients in five study subgroups based on achieved levels of LDL cholesterol: less than 20 mg/dL, 20-49 mg/dL, 50-69 mg/dL, 70-99 mg/dL, and 100 mg/dL or higher. In addition, the rates of both serious adverse events and adverse events leading to study discontinuation was roughly the same in the subgroup of patients with an achieved LDL cholesterol of less than 10 mg/dL as in those with an achieved LDL of at least 100 mg/dL.
Concurrently with Dr. Giugliano’s report, the results also appeared in an online article (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736[17]32290-0).
FOURIER was funded by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and has received research funding from Amgen, and he has also been a consultant to Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Merck, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – The maxim that lower is better for LDL cholesterol continues to hold true, even at jaw-droppingly low levels of less than 10 mg/dL in a new analysis of data from the FOURIER trial.
The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial was the pivotal efficacy and safety study for the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor evolocumab (Repatha) and enrolled patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of at least 70 mg/dL (N Engl J Med. 2017 May 4;376[18]:1713-22).
After a median follow-up of 26 months, the incidence of the study’s primary endpoint (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) dropped by a statistically significant 15% in patients with an achieved LDL cholesterol of 20-49 mg/dL, compared with patients whose 4-week LDL cholesterol was at or above 100 mg/dL (primarily patients randomized to the study’s control arm), by 24% in all patients with LDL cholesterol less than 20 mg/dL, and by 31% in the 2% of patients whose LDL cholesterol levels fell below 10 mg/dL.
These strikingly improved event rates at the lowest levels of LDL cholesterol occurred with no signal of excess adverse events, Robert P. Giugliano, MD, said at the annual congress of the European Society of Cardiology.
In contrast, the 13% of patents whose achieved LDL cholesterol was 50-69 mg/dL had an event rate just 6% below the referent group of 100 mg/dL or more, a nonsignificant difference. Existing cholesterol management guidelines that set LDL cholesterol targets for secondary prevention have used a level below 70 mg/dL as the target, such as the European Society of Cardiology’s 2016 guidelines (Eur Heart J. 2016 Oct 14;37[39]:2999-3058).
“The data suggest that we should target considerably lower LDL cholesterol than is currently recommended for our patients with atherosclerotic cardiovascular disease,” said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Lowest is best with LDL. You don’t need a lot of LDL in the serum for normal human function,” he noted during the discussion of his report.
While FOURIER’s event curve continued to drop as LDL cholesterol fell below 10 mg/dL, the study’s wide-ranging safety assessment showed no signal of harm at the lowest levels. This “gives us some reassurance it’s safe,” he said in an interview. “We saw benefit that continued down to the lowest LDL levels, so it’s hard to pick a LDL target. I no longer feel comfortable treating my patients to just less than 70 mg/dL. I’m not sure what is the optimal LDL target, but I think it needs to be lower than that.”
To achieve such ultralow LDL levels, most patients need treatment with a PCSK9 inhibitor plus at least one and perhaps two additional cholesterol-lowering drugs, a statin and ezetimibe, he noted.
The FOURIER analyses Dr. Giugliano reported included data on the incidence during the study of 10 specific types of adverse events: noncardiovascular death, serious adverse events, adverse events leading to study discontinuation, and new onset of diabetes, cancer, cataract, neurocognitive deficit, significant liver enzyme increase, significant creatine kinase increase, and hemorrhagic stroke. The incidence of each of these was similar among the patients in five study subgroups based on achieved levels of LDL cholesterol: less than 20 mg/dL, 20-49 mg/dL, 50-69 mg/dL, 70-99 mg/dL, and 100 mg/dL or higher. In addition, the rates of both serious adverse events and adverse events leading to study discontinuation was roughly the same in the subgroup of patients with an achieved LDL cholesterol of less than 10 mg/dL as in those with an achieved LDL of at least 100 mg/dL.
Concurrently with Dr. Giugliano’s report, the results also appeared in an online article (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736[17]32290-0).
FOURIER was funded by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and has received research funding from Amgen, and he has also been a consultant to Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Merck, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – The maxim that lower is better for LDL cholesterol continues to hold true, even at jaw-droppingly low levels of less than 10 mg/dL in a new analysis of data from the FOURIER trial.
The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial was the pivotal efficacy and safety study for the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor evolocumab (Repatha) and enrolled patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of at least 70 mg/dL (N Engl J Med. 2017 May 4;376[18]:1713-22).
After a median follow-up of 26 months, the incidence of the study’s primary endpoint (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) dropped by a statistically significant 15% in patients with an achieved LDL cholesterol of 20-49 mg/dL, compared with patients whose 4-week LDL cholesterol was at or above 100 mg/dL (primarily patients randomized to the study’s control arm), by 24% in all patients with LDL cholesterol less than 20 mg/dL, and by 31% in the 2% of patients whose LDL cholesterol levels fell below 10 mg/dL.
These strikingly improved event rates at the lowest levels of LDL cholesterol occurred with no signal of excess adverse events, Robert P. Giugliano, MD, said at the annual congress of the European Society of Cardiology.
In contrast, the 13% of patents whose achieved LDL cholesterol was 50-69 mg/dL had an event rate just 6% below the referent group of 100 mg/dL or more, a nonsignificant difference. Existing cholesterol management guidelines that set LDL cholesterol targets for secondary prevention have used a level below 70 mg/dL as the target, such as the European Society of Cardiology’s 2016 guidelines (Eur Heart J. 2016 Oct 14;37[39]:2999-3058).
“The data suggest that we should target considerably lower LDL cholesterol than is currently recommended for our patients with atherosclerotic cardiovascular disease,” said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston.
“Lowest is best with LDL. You don’t need a lot of LDL in the serum for normal human function,” he noted during the discussion of his report.
While FOURIER’s event curve continued to drop as LDL cholesterol fell below 10 mg/dL, the study’s wide-ranging safety assessment showed no signal of harm at the lowest levels. This “gives us some reassurance it’s safe,” he said in an interview. “We saw benefit that continued down to the lowest LDL levels, so it’s hard to pick a LDL target. I no longer feel comfortable treating my patients to just less than 70 mg/dL. I’m not sure what is the optimal LDL target, but I think it needs to be lower than that.”
To achieve such ultralow LDL levels, most patients need treatment with a PCSK9 inhibitor plus at least one and perhaps two additional cholesterol-lowering drugs, a statin and ezetimibe, he noted.
The FOURIER analyses Dr. Giugliano reported included data on the incidence during the study of 10 specific types of adverse events: noncardiovascular death, serious adverse events, adverse events leading to study discontinuation, and new onset of diabetes, cancer, cataract, neurocognitive deficit, significant liver enzyme increase, significant creatine kinase increase, and hemorrhagic stroke. The incidence of each of these was similar among the patients in five study subgroups based on achieved levels of LDL cholesterol: less than 20 mg/dL, 20-49 mg/dL, 50-69 mg/dL, 70-99 mg/dL, and 100 mg/dL or higher. In addition, the rates of both serious adverse events and adverse events leading to study discontinuation was roughly the same in the subgroup of patients with an achieved LDL cholesterol of less than 10 mg/dL as in those with an achieved LDL of at least 100 mg/dL.
Concurrently with Dr. Giugliano’s report, the results also appeared in an online article (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736[17]32290-0).
FOURIER was funded by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and has received research funding from Amgen, and he has also been a consultant to Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Merck, and Pfizer.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Patients with an achieved LDL of less than 10 mg/dL had an event rate 31% below patients with an LDL at or above 100 mg/dL.
Data source: FOURIER, an international multicenter trial with 27,564 patients.
Disclosures: FOURIER was funded by Amgen, the company that markets evolocumab (Repatha). Dr. Giugliano has been a consultant to and has received research funding from Amgen, and he has also been a consultant to Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Merck, and Pfizer.
Oral anticoagulation ‘reasonable’ in advanced kidney disease with A-fib
BARCELONA – Oral anticoagulation had a net overall benefit for patients with atrial fibrillation and advanced chronic kidney disease, based on results of a large observational study reported at the annual congress of the European Society of Cardiology.
The novel direct-acting oral anticoagulants (NOACs) and warfarin were all similarly effective in this study of 39,241 patients who had stage 4 or 5 chronic kidney disease (CKD), atrial fibrillation, and were not on dialysis. Compared with no oral anticoagulation, the drugs cut in half the risk of stroke or systemic embolism, with no increased risk of major bleeding.
“In patients with advanced CKD, it appears that OACs [oral anticoagulants] are reasonable,” concluded Peter A. Noseworthy, MD, of the Mayo Clinic in Rochester, Minn.
This is a potentially practice-changing finding given the “striking underutilization” of OACs in advanced CKD, he noted. Indeed, only one-third of the patients in this study were prescribed an OAC and picked up their prescriptions. And while the study has the limitations inherent to an observational study reliant upon data from a large U.S. administrative database – chiefly, the potential for residual confounding because of factors that couldn’t be adjusted for statistically – these real-world data may be as good as it gets, since patients with advanced CKD were excluded from the pivotal trials of the NOACs.
Apixaban (Eliquis) was the winner in this study: It separated itself from the pack by reducing the major bleeding risk by 57%, compared with warfarin, although it wasn’t significantly more effective than the other drugs in terms of stroke prevention. In contrast, the major bleeding rates for dabigatran (Pradaxa) and rivaroxaban (Xarelto) weren’t significantly different from warfarin in this challenging patient population.
In a related analysis of 10,712 patients with atrial fibrillation and advanced CKD who were on dialysis, use of an OAC was once again a winning strategy: It resulted not only in an impressive 58% reduction in the risk of stroke or systemic embolism, but also a 26% reduction in the risk of major bleeding, compared with no OAC.
Here again, apixaban was arguably the drug of choice. None of the 125 dialysis patients on apixaban experienced a stroke or systemic embolism. In contrast, dabigatran and rivaroxaban were associated with greater than threefold higher stroke rates than in patients on warfarin, although these differences didn’t achieve statistical significance because of small numbers, just 36 patients on dabigatran and 56 on rivaroxaban, the cardiologist continued.
For these analyses of the relationship between OAC exposure and stroke and bleeding outcomes, Dr. Noseworthy and his coinvestigators used propensity scores based upon 59 clinical and sociodemographic characteristics.
Asked why rates of utilization of OACs are so low in patients with advanced CKD, Dr. Noseworthy replied that he didn’t find that particularly surprising.
“Even if you look only at patients without renal dysfunction, there is incredible undertreatment of atrial fibrillation with OACs. And adherence is very poor,” he observed.
Moreover, in talking with nephrologists, he finds many of them have legitimate reservations about prescribing OACs for patients with end-stage renal disease on hemodialysis.
“They’re undergoing a lot of procedures. They’re having a ton of lines placed; they’re having fistulas revised; and they have very high rates of GI bleeding. In some studies the annual risk of bleeding is 20%-40% in this population. And they’re a frail population with frequent falls,” Dr. Noseworthy said.
He reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Oral anticoagulation had a net overall benefit for patients with atrial fibrillation and advanced chronic kidney disease, based on results of a large observational study reported at the annual congress of the European Society of Cardiology.
The novel direct-acting oral anticoagulants (NOACs) and warfarin were all similarly effective in this study of 39,241 patients who had stage 4 or 5 chronic kidney disease (CKD), atrial fibrillation, and were not on dialysis. Compared with no oral anticoagulation, the drugs cut in half the risk of stroke or systemic embolism, with no increased risk of major bleeding.
“In patients with advanced CKD, it appears that OACs [oral anticoagulants] are reasonable,” concluded Peter A. Noseworthy, MD, of the Mayo Clinic in Rochester, Minn.
This is a potentially practice-changing finding given the “striking underutilization” of OACs in advanced CKD, he noted. Indeed, only one-third of the patients in this study were prescribed an OAC and picked up their prescriptions. And while the study has the limitations inherent to an observational study reliant upon data from a large U.S. administrative database – chiefly, the potential for residual confounding because of factors that couldn’t be adjusted for statistically – these real-world data may be as good as it gets, since patients with advanced CKD were excluded from the pivotal trials of the NOACs.
Apixaban (Eliquis) was the winner in this study: It separated itself from the pack by reducing the major bleeding risk by 57%, compared with warfarin, although it wasn’t significantly more effective than the other drugs in terms of stroke prevention. In contrast, the major bleeding rates for dabigatran (Pradaxa) and rivaroxaban (Xarelto) weren’t significantly different from warfarin in this challenging patient population.
In a related analysis of 10,712 patients with atrial fibrillation and advanced CKD who were on dialysis, use of an OAC was once again a winning strategy: It resulted not only in an impressive 58% reduction in the risk of stroke or systemic embolism, but also a 26% reduction in the risk of major bleeding, compared with no OAC.
Here again, apixaban was arguably the drug of choice. None of the 125 dialysis patients on apixaban experienced a stroke or systemic embolism. In contrast, dabigatran and rivaroxaban were associated with greater than threefold higher stroke rates than in patients on warfarin, although these differences didn’t achieve statistical significance because of small numbers, just 36 patients on dabigatran and 56 on rivaroxaban, the cardiologist continued.
For these analyses of the relationship between OAC exposure and stroke and bleeding outcomes, Dr. Noseworthy and his coinvestigators used propensity scores based upon 59 clinical and sociodemographic characteristics.
Asked why rates of utilization of OACs are so low in patients with advanced CKD, Dr. Noseworthy replied that he didn’t find that particularly surprising.
“Even if you look only at patients without renal dysfunction, there is incredible undertreatment of atrial fibrillation with OACs. And adherence is very poor,” he observed.
Moreover, in talking with nephrologists, he finds many of them have legitimate reservations about prescribing OACs for patients with end-stage renal disease on hemodialysis.
“They’re undergoing a lot of procedures. They’re having a ton of lines placed; they’re having fistulas revised; and they have very high rates of GI bleeding. In some studies the annual risk of bleeding is 20%-40% in this population. And they’re a frail population with frequent falls,” Dr. Noseworthy said.
He reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Oral anticoagulation had a net overall benefit for patients with atrial fibrillation and advanced chronic kidney disease, based on results of a large observational study reported at the annual congress of the European Society of Cardiology.
The novel direct-acting oral anticoagulants (NOACs) and warfarin were all similarly effective in this study of 39,241 patients who had stage 4 or 5 chronic kidney disease (CKD), atrial fibrillation, and were not on dialysis. Compared with no oral anticoagulation, the drugs cut in half the risk of stroke or systemic embolism, with no increased risk of major bleeding.
“In patients with advanced CKD, it appears that OACs [oral anticoagulants] are reasonable,” concluded Peter A. Noseworthy, MD, of the Mayo Clinic in Rochester, Minn.
This is a potentially practice-changing finding given the “striking underutilization” of OACs in advanced CKD, he noted. Indeed, only one-third of the patients in this study were prescribed an OAC and picked up their prescriptions. And while the study has the limitations inherent to an observational study reliant upon data from a large U.S. administrative database – chiefly, the potential for residual confounding because of factors that couldn’t be adjusted for statistically – these real-world data may be as good as it gets, since patients with advanced CKD were excluded from the pivotal trials of the NOACs.
Apixaban (Eliquis) was the winner in this study: It separated itself from the pack by reducing the major bleeding risk by 57%, compared with warfarin, although it wasn’t significantly more effective than the other drugs in terms of stroke prevention. In contrast, the major bleeding rates for dabigatran (Pradaxa) and rivaroxaban (Xarelto) weren’t significantly different from warfarin in this challenging patient population.
In a related analysis of 10,712 patients with atrial fibrillation and advanced CKD who were on dialysis, use of an OAC was once again a winning strategy: It resulted not only in an impressive 58% reduction in the risk of stroke or systemic embolism, but also a 26% reduction in the risk of major bleeding, compared with no OAC.
Here again, apixaban was arguably the drug of choice. None of the 125 dialysis patients on apixaban experienced a stroke or systemic embolism. In contrast, dabigatran and rivaroxaban were associated with greater than threefold higher stroke rates than in patients on warfarin, although these differences didn’t achieve statistical significance because of small numbers, just 36 patients on dabigatran and 56 on rivaroxaban, the cardiologist continued.
For these analyses of the relationship between OAC exposure and stroke and bleeding outcomes, Dr. Noseworthy and his coinvestigators used propensity scores based upon 59 clinical and sociodemographic characteristics.
Asked why rates of utilization of OACs are so low in patients with advanced CKD, Dr. Noseworthy replied that he didn’t find that particularly surprising.
“Even if you look only at patients without renal dysfunction, there is incredible undertreatment of atrial fibrillation with OACs. And adherence is very poor,” he observed.
Moreover, in talking with nephrologists, he finds many of them have legitimate reservations about prescribing OACs for patients with end-stage renal disease on hemodialysis.
“They’re undergoing a lot of procedures. They’re having a ton of lines placed; they’re having fistulas revised; and they have very high rates of GI bleeding. In some studies the annual risk of bleeding is 20%-40% in this population. And they’re a frail population with frequent falls,” Dr. Noseworthy said.
He reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The risk of stroke/systemic embolism in patients with advanced chronic kidney disease who were on oral anticoagulation was reduced by 49% among those not on hemodialysis and by 58% in those who were, compared with similar patients not on oral anticoagulation.
Data source: This was an observational study of nearly 50,000 patients with atrial fibrillation and stage 4 or 5 chronic kidney disease in a large U.S. administrative database.
Disclosures: The presenter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
VIDEO: Educational intervention boosts A fib anticoagulation
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
IMPACT AF is an important study, with impressive results that confirm the value of integrated atrial fibrillation care. In the study, a comprehensive and continuous educational intervention with 11 distinct components aimed at health care professionals and patients increased the initiation of and adherence to oral anticoagulation in patients with AF. This effect linked with a significantly reduced incidence of strokes.
Digital tools are an important part of the intervention. They provide both information and feedback, and they create a platform that can involve all stakeholders in management of atrial fibrillation. Informing AF patients about their treatment can result in patients who take responsibility for their management. Integrated AF management models can improve continued delivery of chronic care.
Paulus Kirchhof, MD , is a professor and deputy director of the Institute of Cardiovascular Sciences at the University of Birmingham, England. He has received honoraria and research funding from several drug companies. He made these comments as designated discussant for the report.
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.
Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.
The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”
IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.
In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.
Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.
During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).
“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.
IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Anticoagulation rose by 12 percentage points from baseline with intervention and by 3 percentage points among controls.
Data source: IMPACT AF, which randomized 2,281 AF patients for 1 year at 48 centers in five middle-income countries.
Disclosures: IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.
Older men benefit from vascular screening
BARCELONA – Population screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension targeted to men aged 65-74 years saved lives in a highly cost-effective way in a Danish randomized study of more than 50,000 men.
During a median follow-up of 4.4 years, total mortality was 7% lower among men invited for this triple-screening panel, compared with uninvited controls – a statistically significant difference achieved without causing any identified serious adverse effects. The cost ran 2,148 euro (about $2,600) per quality adjusted year, making it very “cost attractive,” Jes S. Lindholt, DMSci, said at the annual congress of the European Society of Cardiology.
Dr. Lindholt also said that ongoing studies are assessing the clinical- and cost- effectiveness of screening for AAA and PAD in women in a targeted age range. But for the time being, “we believe the greatest benefit is in men.”
The Viborg Vascular (VIVA) screening trial (ClinicalTrials.gov NCT00662480) randomized all 50,156 men aged 65-74 years living in the central region of Denmark to either receive an invitation to triple disease screening or to receive no invitation and form the control group. Three-quarters of those invited for screening came to screening clinics at 14 regional centers. The examinations identified an AAA in 3%, PAD in 11%, and hypertension in 10%. About a third of people identified with AAA or PAD started treatment with aspirin, a statin, or both, and a small number of those with an AAA underwent surgical repair during the following 5 years. About a third of those newly diagnosed with hypertension began treatment with antihypertensive drugs.
The results showed that for every 169 men invited for screening the program saved one life during follow-up, compared with men in the control arm. “To our knowledge, no prior population-based screening program has shown an impact on overall mortality,” Dr. Lindholt said. Concurrently with his report, the results appeared online (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736(17)32250-X).
VIVA received no commercial funding. Dr. Lindholt had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Triple screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension is a good idea, and the new results from the VIVA trial serve as a call for broader screening initiatives.
Although the patients identified with one or more of the conditions screened received a relatively low rate of interventions, the program nonetheless produced a net benefit. The cost effectiveness of screening was very acceptable, and could potentially further improve if people identified with disease receive treatment sooner. The data showed a modest impact on quality of life, but the findings provided assurance that the screening program produced no excess adverse effects and no decrement in quality of life.
The study was also large and had a median follow-up of more than 4 years. The results also showed the risk for overdiagnosis was no worse than is seen with breast cancer screening.
Andrew M. Kates, MD , is a cardiologist and professor of medicine at Washington University in St. Louis. He had no disclosures. He made these comments as designated discussant for the VIVA trial.
Triple screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension is a good idea, and the new results from the VIVA trial serve as a call for broader screening initiatives.
Although the patients identified with one or more of the conditions screened received a relatively low rate of interventions, the program nonetheless produced a net benefit. The cost effectiveness of screening was very acceptable, and could potentially further improve if people identified with disease receive treatment sooner. The data showed a modest impact on quality of life, but the findings provided assurance that the screening program produced no excess adverse effects and no decrement in quality of life.
The study was also large and had a median follow-up of more than 4 years. The results also showed the risk for overdiagnosis was no worse than is seen with breast cancer screening.
Andrew M. Kates, MD , is a cardiologist and professor of medicine at Washington University in St. Louis. He had no disclosures. He made these comments as designated discussant for the VIVA trial.
Triple screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension is a good idea, and the new results from the VIVA trial serve as a call for broader screening initiatives.
Although the patients identified with one or more of the conditions screened received a relatively low rate of interventions, the program nonetheless produced a net benefit. The cost effectiveness of screening was very acceptable, and could potentially further improve if people identified with disease receive treatment sooner. The data showed a modest impact on quality of life, but the findings provided assurance that the screening program produced no excess adverse effects and no decrement in quality of life.
The study was also large and had a median follow-up of more than 4 years. The results also showed the risk for overdiagnosis was no worse than is seen with breast cancer screening.
Andrew M. Kates, MD , is a cardiologist and professor of medicine at Washington University in St. Louis. He had no disclosures. He made these comments as designated discussant for the VIVA trial.
BARCELONA – Population screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension targeted to men aged 65-74 years saved lives in a highly cost-effective way in a Danish randomized study of more than 50,000 men.
During a median follow-up of 4.4 years, total mortality was 7% lower among men invited for this triple-screening panel, compared with uninvited controls – a statistically significant difference achieved without causing any identified serious adverse effects. The cost ran 2,148 euro (about $2,600) per quality adjusted year, making it very “cost attractive,” Jes S. Lindholt, DMSci, said at the annual congress of the European Society of Cardiology.
Dr. Lindholt also said that ongoing studies are assessing the clinical- and cost- effectiveness of screening for AAA and PAD in women in a targeted age range. But for the time being, “we believe the greatest benefit is in men.”
The Viborg Vascular (VIVA) screening trial (ClinicalTrials.gov NCT00662480) randomized all 50,156 men aged 65-74 years living in the central region of Denmark to either receive an invitation to triple disease screening or to receive no invitation and form the control group. Three-quarters of those invited for screening came to screening clinics at 14 regional centers. The examinations identified an AAA in 3%, PAD in 11%, and hypertension in 10%. About a third of people identified with AAA or PAD started treatment with aspirin, a statin, or both, and a small number of those with an AAA underwent surgical repair during the following 5 years. About a third of those newly diagnosed with hypertension began treatment with antihypertensive drugs.
The results showed that for every 169 men invited for screening the program saved one life during follow-up, compared with men in the control arm. “To our knowledge, no prior population-based screening program has shown an impact on overall mortality,” Dr. Lindholt said. Concurrently with his report, the results appeared online (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736(17)32250-X).
VIVA received no commercial funding. Dr. Lindholt had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – Population screening for abdominal aortic aneurysms, peripheral arterial disease, and hypertension targeted to men aged 65-74 years saved lives in a highly cost-effective way in a Danish randomized study of more than 50,000 men.
During a median follow-up of 4.4 years, total mortality was 7% lower among men invited for this triple-screening panel, compared with uninvited controls – a statistically significant difference achieved without causing any identified serious adverse effects. The cost ran 2,148 euro (about $2,600) per quality adjusted year, making it very “cost attractive,” Jes S. Lindholt, DMSci, said at the annual congress of the European Society of Cardiology.
Dr. Lindholt also said that ongoing studies are assessing the clinical- and cost- effectiveness of screening for AAA and PAD in women in a targeted age range. But for the time being, “we believe the greatest benefit is in men.”
The Viborg Vascular (VIVA) screening trial (ClinicalTrials.gov NCT00662480) randomized all 50,156 men aged 65-74 years living in the central region of Denmark to either receive an invitation to triple disease screening or to receive no invitation and form the control group. Three-quarters of those invited for screening came to screening clinics at 14 regional centers. The examinations identified an AAA in 3%, PAD in 11%, and hypertension in 10%. About a third of people identified with AAA or PAD started treatment with aspirin, a statin, or both, and a small number of those with an AAA underwent surgical repair during the following 5 years. About a third of those newly diagnosed with hypertension began treatment with antihypertensive drugs.
The results showed that for every 169 men invited for screening the program saved one life during follow-up, compared with men in the control arm. “To our knowledge, no prior population-based screening program has shown an impact on overall mortality,” Dr. Lindholt said. Concurrently with his report, the results appeared online (Lancet. 2017 Aug 28. doi: 10.1016/S0140-6736(17)32250-X).
VIVA received no commercial funding. Dr. Lindholt had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Overall mortality during median follow-up of 4 years was 7% lower among men invited to screening, compared with unscreened controls.
Data source: VIVA, a randomized, multicenter trial of 50,156 Danish men.
Disclosures: VIVA received no commercial funding. Dr. Lindholt had no disclosures.
Ivabradine cut mortality in HFrEF patients not on beta-blocker
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: All-cause mortality was reduced by 30%, compared with placebo, in ivabradine-treated patients with heart failure with reduced ejection fraction who were not on a beta-blocker.
Data source: A post-hoc analysis of the 685 patients in a much larger randomized, placebo-controlled clinical trial of ivabradine in patients with heart failure with reduced ejection fraction.
Disclosures: The SHIFT trial was funded by Servier. The presenter reported serving as a consultant to and recipient of research grants from that and other companies.
Preventive upstream therapy prevents progression of atrial fib
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic. 
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: At 1 year, 75% of patients with baseline persistent atrial fibrillation who received a four-pronged program of upstream risk factor modification were in sinus rhythm, compared with 63% of controls.
Data source: RACE 3 was a multicenter, randomized, nonblinded clinical trial including 245 patients with a recent history of persistent atrial fibrillation and heart failure.
Disclosures: The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. The presenter reported having no relevant financial interests.
A Fib ablation surpasses drugs for improving quality of life
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: After 12 months, average SF-36 scores improved by 11 points with ablation and 3 points with drug therapy.
Data source: CAPTAF, a multicenter, randomized trial with 155 patients.
Disclosures: CAPTAF received partial funding from Medtronic. Dr. Blomström-Lundqvist has received research funding from Medtronic and Cardiome, and she has received honoraria for speaking from Medtronic and also from Bayer, Biotronik, Bristol-Myers Squibb, Merck, Pfizer, and Sanofi. Dr. Bueno has been a consultant to Abbott, Bayer, Bristol-Myers Squibb, Ferrer, Novartis, Pfizer, and Servier, and has received research funding from AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis.
VIDEO: Clopidogrel bests ticagrelor in PCI for ACS in real-world study
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
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“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
BARCELONA – Patients who underwent percutaneous coronary intervention for acute coronary syndrome using newer-generation drug-eluting stents backed by ticagrelor-based dual-antiplatelet therapy had significantly higher net adverse event rates at 1 year than did those with clopidogrel-based DAPT in the CHANGE DAPT study, Clemens von Birgelen, MD, reported at the annual congress of the European Society of Cardiology.
Based upon the CHANGE DAPT findings and those from other recent studies, it would be appropriate to revise ESC and American College of Cardiology/American Heart Association guidelines, which now give the newer, more potent platelet inhibitors ticagrelor (Brilinta) or prasugrel (Effient) preferential status as the P2Y12 inhibitor of choice over clopidogrel, added Dr. von Birgelen, professor of cardiology at the University of Twente in Enschede, the Netherlands, and codirector of the department of cardiology at Thoraxcentrum Twente.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“With the newer drug-eluting stents we see lower ischemic event rates, so the DAPT side effects due to bleeding become more important at this time. It could be that patients with ACS who are undergoing PCI may no longer need the most potent DAPT. Perhaps less potent DAPT with clopidogrel may be sufficient when using these more modern devices,” Dr. von Birgelen said in an interview.
CHANGE DAPT was a prospective, observational registry study that compared 1-year clinical outcomes in 2,062 consecutive ACS patients treated by PCI at Thoraxcentrum Twente, a high-volume PCI center. Half of the patients were treated before the primary DAPT regimen in the region changed from clopidogrel-based to ticagrelor-based DAPT on May 1, 2014, while the other half underwent PCI after the switch. This unique registry study design avoids selection bias, whereby cardiologists might preferentially use clopidogrel – the less potent P2Y12 inhibitor – in frailer patients.
The primary endpoint was the 1-year composite of all-cause mortality, any MI, stroke, or major bleeding. The rate was 7.8% in the ticagrelor period and significantly lower at 5.1% in the clopidogrel period. This difference was driven by the significantly lower major bleeding rate in the clopidogrel group: 1.2% versus 2.7% with ticagrelor-based DAPT.
The increased risk of bleeding associated with ticagrelor wasn’t offset by any advantage in term of ischemic events; indeed, the rate of such events was actually numerically lower with clopidogrel-based DAPT, albeit not statistically significantly so. Definite or probable stent thrombosis occurred in 0.6% of the clopidogrel group and 0.8% of the ticagrelor group, while the composite of cardiac death, MI, or stroke occurred in 3.7% of patients on clopidogrel-based DAPT compared with 4.7% on ticagrelor.
The two patient groups were closely similar at baseline in most respects, although the ticagrelor group was, on average, 1 year older, reflecting the more recent increased willingness of interventional cardiologists to utilize PCI in patients of advanced age. In terms of procedural differences, the ticagrelor group was more likely to undergo a transradial rather than transfemoral approach, less likely to receive a glycoprotein IIb/IIIa inhibitor, and more likely to get a proton pump inhibitor.
“All three of those factors should have reduced the bleeding risk during that second period,” Dr. von Birgelen observed.
In a propensity score–adjusted analysis taking account of the few between-group differences, ticagrelor-based DAPT was associated with a 1.75-fold increased risk of the primary endpoint and a 2.75-fold increased risk of major bleeding.
He noted that the CHANGE DAPT results are consistent with those of TOPIC, a 646-patient, single-center randomized trial conducted in Marseille. In TOPIC, after 1 month on ticagrelor- or prasugrel-backed DAPT, half of patients were switched to vastly less expensive clopidogrel for the remaining 11 months of DAPT. The result in the switched group was a marked decrease in bleeding with no increased risk of ischemic events.
“I see our study as a piece in a mosaic of studies and real-world registries with a similar message that have recently been reported,” the cardiologist said. “I hope the ESC looks carefully at these data.”
Session cochair Laura Mauri, MD, said that while it’s important to look at real-world observational data such as CHANGE DAPT to see if the results of randomized trials are generalizable, she’s not surprised by the evidence of increased risk of bleeding with a more potent agent such as ticagrelor.
“Why there’s a lack of benefit demonstrated, I think, is the bigger question,” said Dr. Mauri, professor of medicine at Harvard Medical School, Boston. “It could be related to changes in procedures over time, with procedures being conducted in a more complex manner, or some other residual confounding. I think whenever we see an observational study that changes the nature of the benefit that we see, it needs to be investigated more deeply. I don’t think it’s time to dismiss the results of very large randomized trials that show a meaningful benefit for the potent agents in the setting of ACS.”
CHANGE DAPT was an investigator-initiated study conducted without external funding. Dr. von Birgelen reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The 1-year composite endpoint of all-cause mortality, MI, stroke, or major bleeding occurred in 5.1% of ACS patients who underwent PCI using newer-generation drug-eluting stents followed by clopidogrel-based DAPT, compared with 7.8% who received ticagrelor-based DAPT.
Data source: This unique design for a prospective observational registry study compared 1-year outcomes in 2,062 consecutive ACS patients who underwent PCI at a single high-volume center, half before a regional switch from clopidogrel- to ticagrelor-based DAPT and half afterward.
Disclosures: CHANGE DAPT was an investigator-initiated study conducted without external funding. The presenter reported having no financial conflicts of interest.
Dr. Clyde Yancy: CANTOS wows, opens new therapeutic avenues
BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”
Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.
“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.
“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.
BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”
Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.
“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.
“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.
BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”
Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.
“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.
“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.
AT THE ESC CONGRESS 2017
