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Results from a prospective, multicenter, uncontrolled series of just over 1,500 patients with high bleeding risk who underwent coronary revascularization with a polymer-based, zotarolimus-eluting stent showed that these patients could safely receive dual-antiplatelet therapy (DAPT)for just 1 month.
This finding sets the stage for a new labeled indication for this device and management strategy in this patient population.
Results from the Onyx ONE Clear study “met its primary endpoint, with favorable rates of ischemic outcomes from 1-12 months after DAPT discontinuation within a high risk population of HBR [high-bleeding-risk] patients,” Ajay J. Kirtane, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. The rate of cardiac death or MI during months 1-12 of follow-up while patients were on single-antiplatelet therapy (SAPT) with either aspirin or a P2Y12 inhibitor, usually clopidogrel, was 7.0%, compared with a prespecified performance goal of 9.7% or less, a goal set in consultation with and approval from the Food and Drug Administration based on the results from earlier, short DAPT studies in HBR patients.
“We hope these data will support our submission to the FDA for a 1-month DAPT indication for high-bleeding-risk patients treated with Resolute Onyx,” the polymer-based, zotarolimus-eluting stent tested in the study, said an officer with Medtronic, the company that sponsored this study and markets this stent, in a written statement. Currently, no stent has received a U.S. indication for just 1 month of DAPT treatment.
“The Onyx ONE Clear study represents the largest analysis of 1-month DAPT among commercially available DES [drug-eluting stents], and extends findings from the Onyx ONE [randomized, controlled trial] assuring the safety of a 1-month DAPT strategy among selected patients with high bleeding risk,” said David E. Kandzari, MD, director of interventional cardiology at Piedmont Healthcare in Atlanta and coprincipal investigator for the study along with Dr. Kirtane.
“Despite the patient complexity included in the study, the observation of a favorably low rate of ischemic events despite abbreviated DAPT is consistent with a theme from other contemporary studies that, among HBR patients, bleeding risk rather than ischemic risk should guide clinical decision making regarding DAPT duration,” Dr. Kandzari said in an interview.
Two similar trials
The Onyx ONE Clear results were consistent with findings from a study with a somewhat similar design, LEADERS FREE II, a single-arm study that assessed the safety and efficacy of BioFreedom, a polymer-free umirolimus-coated coronary stent, in HBR patients treated with DAPT for 1 month followed by SAPT.
LEADERS FREE II showed a 12-month cardiac death or MI rate of 8.6% that compared favorably with the 12.3% 1-year rate among similar patients who received bare-metal stents and a similar timing of DAPT and SAPT in a historical control group (Circ Cardiovasc Interv. 2020 Apr 13. doi: 10.1161/CIRCINTERVENTIONS.119.008603). The primary goal of LEADERS FREE II was to serve as the pivotal trial for FDA approval of the BioFreedom stent, but as of May 2020 the FDA had not approved this stent for U.S. use.
Results of another recent study, Onyx ONE, that supplied more than half the patients included in the Onyx ONE Clear analysis, showed that, in a head-to-head comparison of the Onxy and BioFreedom stents in 1,996 HBR patients treated with DAPT for 1 month followed by 11 months of SAPT, the Onyx stent was noninferior for both a primary safety outcome and a secondary efficacy outcome (N Engl J Med. 2020 Mar 26;382[13]:1208-18).
“The major differences” between the Onyx and BioFreedom stents in the patients studied in Onxy ONE Clear and in LEADERS FREE II “lie in the fact that BioFreedom is not approved in the U.S., and that Onyx is a current generation, preferred DES platform for both conventional and HBR patients,” Dr. Kirtane said in an interview.
“Because of the performance characteristics of Onyx, as well as the fact that ONYX ONE studied a far more complex group of patients than other shorter DAPT studies with conventional DES, I personally feel that there will be a preference to use this stent as a result of these data,” added Dr. Kirtane, professor of medicine at Columbia University and director of the coronary catheterization laboratory at New York–Presbyterian Hospital in New York.
The results from Onyx ONE “are critical for changing practice” among U.S. interventionalists, commented Sunil V. Rao, MD, an interventional cardiologist and professor of medicine at Duke University, Durham, N.C. Based on the new findings, U.S. operators performing percutaneous coronary interventions “will feel comfortable stopping DAPT in patients who are at high bleeding risk,” he said in an interview.
Although the results from LEADERS FREE II showed that the BioFreedom stent was superior to a bare-metal stent with 1 month of DAPT in HBR patients, and the results from Onyx ONE showed that the Onyx stent was noninferior to BioFreedom in this setting, “it’s important not to assume that there is a class effect across DES platforms. Each platform has a different drug and different stent design, so the interventional community needs to see these data for each DES,” Dr. Rao maintained.
Onyx ONE Clear design
Onyx ONE Clear enrolled a total of 1,506 patients, including more than 1,000 patients who received the Onyx stent in the Onyx ONE trial and an additional 752 patients enrolled in the United States and Japan, but 263 of these patients had an adverse event during their first 30 days or follow-up leaving 1,506 patients eligible to continue into the Onyx ONE Clear analysis, and with 1,491 patients followed through 12 months. Patients were an average age of 74 years, a little over two-thirds were men, 49% had a recent acute coronary syndrome event and 41% had chronic coronary syndrome. The choice of which antiplatelet agent to continue when patients transitioned to SAPT after 30 days on DAPT was left to the discretion of the physicians for each enrolled patient.
One issue these studies did not address was whether 1 month is the ideal duration for DAPT before switching to SAPT in HBR patients following coronary stenting, or whether longer DAPT durations produce even better outcomes. “It was important to establish what happens if we need to stop DAPT early.” The Onyx ONE and Onyx ONE Clear studies “provide much-needed data informing clinicians of the risks and safety of SAPT after 1 month in appropriately selected patients,” Dr. Kirtane said.
“The results do not indicate that all HBR patients should be treated with 1 month [of] DAPT, but instead demonstrate the safety and effectiveness of this strategy when clinically appropriate.” This scenario “is quite common, given that HBR patients represent up to a third” of patients undergoing percutaneous coronary intervention, Dr. Kandzari said.
Onyx ONE and Onyx ONE Clear were sponsored by Medtronic, the company that markets the Onyx coronary stent. Dr. Kirtane’s institution has received research support from Medtronic, and from Abbott Vascular, Abiomed, Boston Scientific, Cathworks, CSI, Philips, ReCor Medical, and Siemens. Dr. Kandzari has received personal fees and research grants from medtronic, personal fees from Biotronik and Cardiovascular Systems, and research grants from Biotronik, Boston Scientific, and Cardiovascular Systems. Dr. Rao has received personal fees from Medtronic, as well as from CSI and Philips.
SOURCE: Kirtane AJ et al. ACC 2020, Abstract 903-06.
Results from a prospective, multicenter, uncontrolled series of just over 1,500 patients with high bleeding risk who underwent coronary revascularization with a polymer-based, zotarolimus-eluting stent showed that these patients could safely receive dual-antiplatelet therapy (DAPT)for just 1 month.
This finding sets the stage for a new labeled indication for this device and management strategy in this patient population.
Results from the Onyx ONE Clear study “met its primary endpoint, with favorable rates of ischemic outcomes from 1-12 months after DAPT discontinuation within a high risk population of HBR [high-bleeding-risk] patients,” Ajay J. Kirtane, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. The rate of cardiac death or MI during months 1-12 of follow-up while patients were on single-antiplatelet therapy (SAPT) with either aspirin or a P2Y12 inhibitor, usually clopidogrel, was 7.0%, compared with a prespecified performance goal of 9.7% or less, a goal set in consultation with and approval from the Food and Drug Administration based on the results from earlier, short DAPT studies in HBR patients.
“We hope these data will support our submission to the FDA for a 1-month DAPT indication for high-bleeding-risk patients treated with Resolute Onyx,” the polymer-based, zotarolimus-eluting stent tested in the study, said an officer with Medtronic, the company that sponsored this study and markets this stent, in a written statement. Currently, no stent has received a U.S. indication for just 1 month of DAPT treatment.
“The Onyx ONE Clear study represents the largest analysis of 1-month DAPT among commercially available DES [drug-eluting stents], and extends findings from the Onyx ONE [randomized, controlled trial] assuring the safety of a 1-month DAPT strategy among selected patients with high bleeding risk,” said David E. Kandzari, MD, director of interventional cardiology at Piedmont Healthcare in Atlanta and coprincipal investigator for the study along with Dr. Kirtane.
“Despite the patient complexity included in the study, the observation of a favorably low rate of ischemic events despite abbreviated DAPT is consistent with a theme from other contemporary studies that, among HBR patients, bleeding risk rather than ischemic risk should guide clinical decision making regarding DAPT duration,” Dr. Kandzari said in an interview.
Two similar trials
The Onyx ONE Clear results were consistent with findings from a study with a somewhat similar design, LEADERS FREE II, a single-arm study that assessed the safety and efficacy of BioFreedom, a polymer-free umirolimus-coated coronary stent, in HBR patients treated with DAPT for 1 month followed by SAPT.
LEADERS FREE II showed a 12-month cardiac death or MI rate of 8.6% that compared favorably with the 12.3% 1-year rate among similar patients who received bare-metal stents and a similar timing of DAPT and SAPT in a historical control group (Circ Cardiovasc Interv. 2020 Apr 13. doi: 10.1161/CIRCINTERVENTIONS.119.008603). The primary goal of LEADERS FREE II was to serve as the pivotal trial for FDA approval of the BioFreedom stent, but as of May 2020 the FDA had not approved this stent for U.S. use.
Results of another recent study, Onyx ONE, that supplied more than half the patients included in the Onyx ONE Clear analysis, showed that, in a head-to-head comparison of the Onxy and BioFreedom stents in 1,996 HBR patients treated with DAPT for 1 month followed by 11 months of SAPT, the Onyx stent was noninferior for both a primary safety outcome and a secondary efficacy outcome (N Engl J Med. 2020 Mar 26;382[13]:1208-18).
“The major differences” between the Onyx and BioFreedom stents in the patients studied in Onxy ONE Clear and in LEADERS FREE II “lie in the fact that BioFreedom is not approved in the U.S., and that Onyx is a current generation, preferred DES platform for both conventional and HBR patients,” Dr. Kirtane said in an interview.
“Because of the performance characteristics of Onyx, as well as the fact that ONYX ONE studied a far more complex group of patients than other shorter DAPT studies with conventional DES, I personally feel that there will be a preference to use this stent as a result of these data,” added Dr. Kirtane, professor of medicine at Columbia University and director of the coronary catheterization laboratory at New York–Presbyterian Hospital in New York.
The results from Onyx ONE “are critical for changing practice” among U.S. interventionalists, commented Sunil V. Rao, MD, an interventional cardiologist and professor of medicine at Duke University, Durham, N.C. Based on the new findings, U.S. operators performing percutaneous coronary interventions “will feel comfortable stopping DAPT in patients who are at high bleeding risk,” he said in an interview.
Although the results from LEADERS FREE II showed that the BioFreedom stent was superior to a bare-metal stent with 1 month of DAPT in HBR patients, and the results from Onyx ONE showed that the Onyx stent was noninferior to BioFreedom in this setting, “it’s important not to assume that there is a class effect across DES platforms. Each platform has a different drug and different stent design, so the interventional community needs to see these data for each DES,” Dr. Rao maintained.
Onyx ONE Clear design
Onyx ONE Clear enrolled a total of 1,506 patients, including more than 1,000 patients who received the Onyx stent in the Onyx ONE trial and an additional 752 patients enrolled in the United States and Japan, but 263 of these patients had an adverse event during their first 30 days or follow-up leaving 1,506 patients eligible to continue into the Onyx ONE Clear analysis, and with 1,491 patients followed through 12 months. Patients were an average age of 74 years, a little over two-thirds were men, 49% had a recent acute coronary syndrome event and 41% had chronic coronary syndrome. The choice of which antiplatelet agent to continue when patients transitioned to SAPT after 30 days on DAPT was left to the discretion of the physicians for each enrolled patient.
One issue these studies did not address was whether 1 month is the ideal duration for DAPT before switching to SAPT in HBR patients following coronary stenting, or whether longer DAPT durations produce even better outcomes. “It was important to establish what happens if we need to stop DAPT early.” The Onyx ONE and Onyx ONE Clear studies “provide much-needed data informing clinicians of the risks and safety of SAPT after 1 month in appropriately selected patients,” Dr. Kirtane said.
“The results do not indicate that all HBR patients should be treated with 1 month [of] DAPT, but instead demonstrate the safety and effectiveness of this strategy when clinically appropriate.” This scenario “is quite common, given that HBR patients represent up to a third” of patients undergoing percutaneous coronary intervention, Dr. Kandzari said.
Onyx ONE and Onyx ONE Clear were sponsored by Medtronic, the company that markets the Onyx coronary stent. Dr. Kirtane’s institution has received research support from Medtronic, and from Abbott Vascular, Abiomed, Boston Scientific, Cathworks, CSI, Philips, ReCor Medical, and Siemens. Dr. Kandzari has received personal fees and research grants from medtronic, personal fees from Biotronik and Cardiovascular Systems, and research grants from Biotronik, Boston Scientific, and Cardiovascular Systems. Dr. Rao has received personal fees from Medtronic, as well as from CSI and Philips.
SOURCE: Kirtane AJ et al. ACC 2020, Abstract 903-06.
Results from a prospective, multicenter, uncontrolled series of just over 1,500 patients with high bleeding risk who underwent coronary revascularization with a polymer-based, zotarolimus-eluting stent showed that these patients could safely receive dual-antiplatelet therapy (DAPT)for just 1 month.
This finding sets the stage for a new labeled indication for this device and management strategy in this patient population.
Results from the Onyx ONE Clear study “met its primary endpoint, with favorable rates of ischemic outcomes from 1-12 months after DAPT discontinuation within a high risk population of HBR [high-bleeding-risk] patients,” Ajay J. Kirtane, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. The rate of cardiac death or MI during months 1-12 of follow-up while patients were on single-antiplatelet therapy (SAPT) with either aspirin or a P2Y12 inhibitor, usually clopidogrel, was 7.0%, compared with a prespecified performance goal of 9.7% or less, a goal set in consultation with and approval from the Food and Drug Administration based on the results from earlier, short DAPT studies in HBR patients.
“We hope these data will support our submission to the FDA for a 1-month DAPT indication for high-bleeding-risk patients treated with Resolute Onyx,” the polymer-based, zotarolimus-eluting stent tested in the study, said an officer with Medtronic, the company that sponsored this study and markets this stent, in a written statement. Currently, no stent has received a U.S. indication for just 1 month of DAPT treatment.
“The Onyx ONE Clear study represents the largest analysis of 1-month DAPT among commercially available DES [drug-eluting stents], and extends findings from the Onyx ONE [randomized, controlled trial] assuring the safety of a 1-month DAPT strategy among selected patients with high bleeding risk,” said David E. Kandzari, MD, director of interventional cardiology at Piedmont Healthcare in Atlanta and coprincipal investigator for the study along with Dr. Kirtane.
“Despite the patient complexity included in the study, the observation of a favorably low rate of ischemic events despite abbreviated DAPT is consistent with a theme from other contemporary studies that, among HBR patients, bleeding risk rather than ischemic risk should guide clinical decision making regarding DAPT duration,” Dr. Kandzari said in an interview.
Two similar trials
The Onyx ONE Clear results were consistent with findings from a study with a somewhat similar design, LEADERS FREE II, a single-arm study that assessed the safety and efficacy of BioFreedom, a polymer-free umirolimus-coated coronary stent, in HBR patients treated with DAPT for 1 month followed by SAPT.
LEADERS FREE II showed a 12-month cardiac death or MI rate of 8.6% that compared favorably with the 12.3% 1-year rate among similar patients who received bare-metal stents and a similar timing of DAPT and SAPT in a historical control group (Circ Cardiovasc Interv. 2020 Apr 13. doi: 10.1161/CIRCINTERVENTIONS.119.008603). The primary goal of LEADERS FREE II was to serve as the pivotal trial for FDA approval of the BioFreedom stent, but as of May 2020 the FDA had not approved this stent for U.S. use.
Results of another recent study, Onyx ONE, that supplied more than half the patients included in the Onyx ONE Clear analysis, showed that, in a head-to-head comparison of the Onxy and BioFreedom stents in 1,996 HBR patients treated with DAPT for 1 month followed by 11 months of SAPT, the Onyx stent was noninferior for both a primary safety outcome and a secondary efficacy outcome (N Engl J Med. 2020 Mar 26;382[13]:1208-18).
“The major differences” between the Onyx and BioFreedom stents in the patients studied in Onxy ONE Clear and in LEADERS FREE II “lie in the fact that BioFreedom is not approved in the U.S., and that Onyx is a current generation, preferred DES platform for both conventional and HBR patients,” Dr. Kirtane said in an interview.
“Because of the performance characteristics of Onyx, as well as the fact that ONYX ONE studied a far more complex group of patients than other shorter DAPT studies with conventional DES, I personally feel that there will be a preference to use this stent as a result of these data,” added Dr. Kirtane, professor of medicine at Columbia University and director of the coronary catheterization laboratory at New York–Presbyterian Hospital in New York.
The results from Onyx ONE “are critical for changing practice” among U.S. interventionalists, commented Sunil V. Rao, MD, an interventional cardiologist and professor of medicine at Duke University, Durham, N.C. Based on the new findings, U.S. operators performing percutaneous coronary interventions “will feel comfortable stopping DAPT in patients who are at high bleeding risk,” he said in an interview.
Although the results from LEADERS FREE II showed that the BioFreedom stent was superior to a bare-metal stent with 1 month of DAPT in HBR patients, and the results from Onyx ONE showed that the Onyx stent was noninferior to BioFreedom in this setting, “it’s important not to assume that there is a class effect across DES platforms. Each platform has a different drug and different stent design, so the interventional community needs to see these data for each DES,” Dr. Rao maintained.
Onyx ONE Clear design
Onyx ONE Clear enrolled a total of 1,506 patients, including more than 1,000 patients who received the Onyx stent in the Onyx ONE trial and an additional 752 patients enrolled in the United States and Japan, but 263 of these patients had an adverse event during their first 30 days or follow-up leaving 1,506 patients eligible to continue into the Onyx ONE Clear analysis, and with 1,491 patients followed through 12 months. Patients were an average age of 74 years, a little over two-thirds were men, 49% had a recent acute coronary syndrome event and 41% had chronic coronary syndrome. The choice of which antiplatelet agent to continue when patients transitioned to SAPT after 30 days on DAPT was left to the discretion of the physicians for each enrolled patient.
One issue these studies did not address was whether 1 month is the ideal duration for DAPT before switching to SAPT in HBR patients following coronary stenting, or whether longer DAPT durations produce even better outcomes. “It was important to establish what happens if we need to stop DAPT early.” The Onyx ONE and Onyx ONE Clear studies “provide much-needed data informing clinicians of the risks and safety of SAPT after 1 month in appropriately selected patients,” Dr. Kirtane said.
“The results do not indicate that all HBR patients should be treated with 1 month [of] DAPT, but instead demonstrate the safety and effectiveness of this strategy when clinically appropriate.” This scenario “is quite common, given that HBR patients represent up to a third” of patients undergoing percutaneous coronary intervention, Dr. Kandzari said.
Onyx ONE and Onyx ONE Clear were sponsored by Medtronic, the company that markets the Onyx coronary stent. Dr. Kirtane’s institution has received research support from Medtronic, and from Abbott Vascular, Abiomed, Boston Scientific, Cathworks, CSI, Philips, ReCor Medical, and Siemens. Dr. Kandzari has received personal fees and research grants from medtronic, personal fees from Biotronik and Cardiovascular Systems, and research grants from Biotronik, Boston Scientific, and Cardiovascular Systems. Dr. Rao has received personal fees from Medtronic, as well as from CSI and Philips.
SOURCE: Kirtane AJ et al. ACC 2020, Abstract 903-06.
FROM ACC 2020