Shorter Antiplatelet Therapy Course After Stenting May Be Acceptable

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.