Key result
Clopidogrel monotherapy reduces BARC bleeding ~34% versus clopidogrel plus aspirin in ACS with diabetes.
Why the study?
It was unknown whether the benefit of extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy in birisk patients with acute coronary syndromes extends to those with diabetes.
Does clopidogrel monotherapy reduce bleeding compared to continued dual-antiplatelet therapy in birisk patients with acute coronary syndrome and diabetes?
RCT (n=7,758)
1:1
Does clopidogrel monotherapy reduce bleeding compared to continued dual-antiplatelet therapy in birisk patients with acute coronary syndrome and diabetes?
Hazard Ratio: 0.66 (95% CI 0.45–0.97)
Absolute Event Rate: 2.1% vs 3.2%
In birisk ACS patients with diabetes who have completed 9-12 months of DAPT post-PCI, dropping aspirin and continuing clopidogrel monotherapy for 9 months reduces clinically relevant bleeding without increasing ischemic events.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Among ACS patients at high risk for both recurrent ischaemic and bleeding events after PCI who had completed a nine to 12 month standard course of DAPT and were free from major events, a strategy of extended P2Y12 inhibitor monotherapy with clopidogrel for an additional nine months was superior to DAPT with aspirin and clopidogrel for reducing clinically-relevant bleeding and ischaemic events during this period. The increased rate of MACCE in the clopidogrel plus aspirin group was surprising and may be because haemorrhagic events, which are more common with ongoing DAPT, could be associated with an adrenergic state with increased platelet aggregation due to hypotension, remedial procedures to treat bleeding, and the cessation of anti-ischaemic medications.”
“OPT-BIRISK tested an antiplatelet strategy in challenging patients at increased risk for bleeding and ischemic events, but I don't think we can say this is truly a high-risk population.”
“The results provide evidence for this treatment strategy from a large cohort seen in clinical practice in whom the question of continuing DAPT vs. deescalating to clopidogrel monotherapy at this time period has not previously been addressed.”
Subgroup findings in birisk diabetic ACS patients may support extended clopidogrel monotherapy; leaves open confirmation in dedicated trials.
BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.
Journal, society, and media accounts. Useful signal, not independent expert judgment.
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Zhang et al. (2026) conducted an RCT in Acute coronary syndromes at high bleeding and ischemic risk (n=7,758). Clopidogrel monotherapy (clopidogrel plus placebo) vs. Clopidogrel plus aspirin was evaluated on Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization (HR 0.66, 95% CI 0.45-0.97). In birisk patients with ACS and diabetes, clopidogrel monotherapy reduced BARC type 2, 3, or 5 bleeding compared with clopidogrel plus aspirin (2.1% vs 3.2%; HR 0.66; 95% CI 0.45-0.97).