Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.
Zhang D, Li Y, et al. • Journal of the American Heart Association • 2026
In birisk patients with acute coronary syndrome stable on dual-antiplatelet therapy 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.
Key Findings
Results
Clopidogrel monotherapy reduced clinically relevant bleeding in birisk ACS patients with diabetes compared with clopidogrel plus aspirin.
BARC type 2, 3, or 5 bleeding occurred in 2.1% of clopidogrel monotherapy patients versus 3.2% of clopidogrel plus aspirin patients with diabetes.
Hazard ratio for bleeding was 0.66 (95% CI, 0.45–0.97), indicating a statistically significant reduction.
This was the primary endpoint assessed at 9 months after randomization.
Patients had completed 9 to 12 months of dual-antiplatelet therapy prior to randomization.
Results
Clopidogrel monotherapy did not increase major adverse cardiac and cerebral events (MACCE) in birisk ACS patients with diabetes.
MACCE (composite of all-cause death, myocardial infarction, stroke, or clinically driven revascularization) occurred in 2.9% with clopidogrel monotherapy versus 3.6% with clopidogrel plus aspirin in patients with diabetes.
Hazard ratio for MACCE was 0.79 (95% CI, 0.56–1.12), which was not statistically significant.
This was the key secondary endpoint of the analysis.
The confidence interval crossed 1.0, confirming no statistically significant increase in ischemic risk.
Methods
Over half of the OPT-BIRISK trial population had diabetes, making it a clinically important subgroup.
Of 7758 total patients in the trial, 4072 (52.5%) had diabetes.
All patients were classified as both high bleeding risk and high ischemic risk (birisk).
All patients had acute coronary syndrome and had undergone percutaneous coronary intervention.
Patients were randomized 1:1 to clopidogrel plus placebo versus clopidogrel plus aspirin.
Results
The benefits of clopidogrel monotherapy over dual-antiplatelet therapy were consistent regardless of diabetes status, with no significant interaction.
Outcomes were described as 'consistent in patients without diabetes, with no significant interactions by diabetes status.'
This was a prespecified subgroup analysis of the OPT-BIRISK trial (NCT03431142).
The consistency across diabetes and non-diabetes subgroups supports the generalizability of the clopidogrel monotherapy strategy in birisk ACS patients.
Methods
The study design involved randomization to 9 months of extended antiplatelet therapy after an initial 9 to 12 months of dual-antiplatelet therapy post-PCI.
Patients were randomized to clopidogrel plus placebo (monotherapy) or clopidogrel plus aspirin (dual-antiplatelet therapy).
The randomization occurred after patients had already completed 9 to 12 months of DAPT following percutaneous coronary intervention.
The follow-up period for outcomes was 9 months after randomization.
The parent trial, OPT-BIRISK, was registered at ClinicalTrials.gov under identifier NCT03431142.
What This Means
This research looked at whether diabetic patients who have had a heart stent placed after a heart attack can safely switch from taking two blood thinners (clopidogrel plus aspirin) to just one (clopidogrel alone) after about a year of dual therapy. The study analyzed data from over 7,700 patients who were considered 'birisk' — meaning they were at high risk for both dangerous bleeding and dangerous blood clots. More than half of these patients (52.5%) had diabetes, making this a very relevant group to study separately.
The findings showed that among patients with diabetes, switching to clopidogrel alone significantly reduced serious bleeding events (2.1% vs. 3.2%) without causing more heart attacks, strokes, deaths, or need for repeat procedures (2.9% vs. 3.6%). These results were similar in patients without diabetes, and there was no meaningful statistical difference between the two groups, suggesting diabetes status did not change the overall pattern of benefit.
This research suggests that for birisk patients — including those with diabetes — who have been stable on dual blood-thinning therapy for about a year after a stent procedure, dropping aspirin while continuing clopidogrel may reduce bleeding complications without raising the risk of future cardiac events. This is clinically meaningful because people with diabetes are often at higher cardiovascular risk, and physicians may have been hesitant to reduce their antiplatelet therapy. These results could help inform treatment decisions for this common and complex patient population.
Zhang D, Li Y, Qiu M, Zhou Y, Chen S, Pei H, et al.. (2026). Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.049178