An extended 9-month clopidogrel monotherapy regimen was superior to dual antiplatelet therapy (DAPT) in reducing clinically relevant bleeding without increasing ischemic events among acute coronary syndrome (ACS) patients at both high bleeding and ischemic risks (bi-risk) who had already completed 9-12 months of DAPT after drug-eluting stent (DES) implantation, randomized controlled trial data suggest.

Data from the OPT-BIRISK Trial, which compared clopidogrel monotherapy to DAPT, were reported Monday at the European Society of Cardiology (ESC) Congress 2023.

Speaking at ESC 2023 in Amsterdam, Yaling Han, MD, PhD, from the General Hospital of Northern Theater Command, Shenyang, China, noted that antiplatelet therapy can be seen as a “double-edge sword,” whereby there is a lower ischemic risk but a higher bleeding risk – adding that optimal antiplatelet treatment strategies remain a clinical challenge for bi-risk patients.

“Therefore, the aim of this trial was to investigate whether extended clopidogrel monotherapy following routine 9-12 months of DAPT would be safer and have similar anti-ischemic effects compared to the extended DAPT strategy for bi-risk ACS patients who implanted coronary DES,” said Han.

Trial data

The investigator-initiated, multi-center, double-blind, placebo-controlled, randomized trial recruited 7,758 ACS patients across 101 Chinese centers. After 9-12 months DAPT post-PCI, patients were randomized (1-to-1 ratio) to receive either DAPT (clopidogrel plus aspirin; n=3,850) or clopidogrel monotherapy (clopidogrel plus placebo; n = 3,850) for 9 months.

The primary endpoint of the study was clinically relevant bleeding (Bleeding Academic Research Consortium [BARC] type 2, 3 or 5 bleeding) 9 months after randomization, while the secondary endpoint was major adverse cardiac and cerebral events (MACCE) – a composite of all-cause mortality, myocardial infarction (MI), stroke or clinically driven revascularization – 9 months after randomization. Individual components of MACCE, any bleeding, and stent thrombosis were also considered as tertiary endpoints.

Han reported that incidence of BARC type 2, 3 or 5 bleeding occurred in 2.5% of extended monotherapy patients while those randomized for extended DAPT saw a 3.3% incidence – a 25% risk reduction (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.57-0.97; p=0.03), while MACCE was reduced by 26% (3.5% vs. 2.6%; HR 0.74; 95% CI, 0.57-0.96; p=0.02).

She added that the incidence of BARC 3 or 5 bleeding, all-cause death, MI, ischemic stroke, clinically driven revascularization, and stent thrombosis were all similar between the two groups (p>0.05 for all).

“In conclusion, for high-risk ACS patients, who completed 9-12 months of DAPT after DES implantation, an extended 9-month clopidogrel monotherapy regimen was superior to DAPT in reducing clinically relevant bleeding and a major ischemic event,” said Han.

The OPT-BIRISK was supported by National Key R & D Project of China and research grant from Sanofi-Aventis Co. Ltd.

Image Caption: Yaling Han, MD, PhD, speaks during a press conference at the European Society of Cardiology Conference 2023 in Amsterdam. (Screenshot)