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Randomized Controlled Trial
. 2024 Jun 1;9(6):523-531.
doi: 10.1001/jamacardio.2024.0534.

Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial

Yi Li  1 , Jing Li  1 , Bin Wang  1 , Quanmin Jing  1 , Yujie Zeng  2 , Aijie Hou  3 , Zhifang Wang  4 , Aijun Liu  5 , Jinliang Zhang  6 , Yaojun Zhang  7 , Ping Zhang  8 , Daming Jiang  9 , Bin Liu  10 , Jiamao Fan  11 , Jun Zhang  12 , Li Li  13 , Guohai Su  14 , Ming Yang  15 , Weihong Jiang  16 , Peng Qu  17 , Hesong Zeng  18 , Lu Li  19 , Miaohan Qiu  1 , Leisheng Ru  20 , Shaoliang Chen  21 , Yujie Zhou  2 , Shubin Qiao  22 , Gregg W Stone  23 , Dominick J Angiolillo  24 , Yaling Han  1 ; OPT-BIRISK Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial

Yi Li et al. JAMA Cardiol. .

Abstract

Importance: Purinergic receptor P2Y12 (P2Y12) inhibitor monotherapy after a certain period of dual antiplatelet therapy (DAPT) may be an attractive option of maintenance antiplatelet treatment for patients undergoing percutaneous coronary intervention (PCI) who are at both high bleeding and ischemic risk (birisk).

Objective: To determine if extended P2Y12 inhibitor monotherapy with clopidogrel is superior to ongoing DAPT with aspirin and clopidogrel after 9 to 12 months of DAPT after PCI in birisk patients with acute coronary syndromes (ACS).

Design, setting, and participants: This was a multicenter, double-blind, placebo-controlled, randomized clinical trial including birisk patients with ACS who had completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months at 101 China centers between February 2018 and December 2020. Study data were analyzed from April 2023 to May 2023.

Interventions: Patients were randomized either to clopidogrel plus placebo or clopidogrel plus aspirin for an additional 9 months.

Main outcomes and measures: The primary end point was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). The primary end point was tested for superiority, and the MACCE end point was tested for sequential noninferiority and superiority.

Results: A total of 7758 patients (mean [SD] age, 64.8 [9.0] years; 4575 male [59.0%]) were included in this study. The primary end point of BARC types 2, 3, or 5 bleeding occurred in 95 of 3873 patients (2.5%) assigned to clopidogrel plus placebo and 127 of 3885 patients (3.3%) assigned to clopidogrel plus aspirin (hazard ratio [HR], 0.75; 95% CI, 0.57-0.97; difference, -0.8%; 95% CI, -1.6% to -0.1%; P = .03). The incidence of MACCE was 2.6% (101 of 3873 patients) in the clopidogrel plus placebo group and 3.5% (136 of 3885 patients) in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96; difference, -0.9%; 95% CI, -1.7% to -0.1%; P < .001 for noninferiority; P = .02 for superiority).

Conclusions and relevance: Among birisk patients with ACS who completed 9 to 12 months of DAPT after drug-eluting stent implantation and were free from adverse events for at least 6 months before randomization, an extended 9-month clopidogrel monotherapy regimen was superior to continuing DAPT with clopidogrel in reducing clinically relevant bleeding without increasing ischemic events.

Trial registration: ClinicalTrials.gov Identifier: NCT03431142.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Stone reported receiving speaker fees from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; consultant fees from Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, Apollo Therapeutics, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; research funding from Ancora, Cagent, Applied Therapeutics, and Biostar; equity or options from SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; and research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave outside the submitted work. Dr Angiolillo reported receiving consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura and research grants from Amgen, AstraZeneca, Bayer, Biosensors, Celo-Nova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
Figure 2.
Figure 2.. Kaplan-Meier Curves for the Principal 9-Month Study Outcomes
A, Cumulative hazard of Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding. B, Cumulative hazard of major adverse cardiac and cerebral events (MACCE). HR indicates hazard ratio.
See this image and copyright information in PMC

Comment on

References

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