Troponin-stratified outcomes of extended clopidogrel monotherapy versus dual antiplatelet therapy in acute coronary syndrome: insights from the OPT-BIRISK randomized trial

Background Extended clopidogrel monotherapy following dual antiplatelet therapy (DAPT) has demonstrated potential efficacy in patients receiving drug-eluting stents (DES). Purpose This prespecified subgroup analysis of the OPT-BIRISK trial evaluated the safety and efficacy of extended clopidogrel monotherapy versus continued DAPT in acute coronary syndromes (ACS) patients with coexisting high ischemic and bleeding risks, stratified by troponin status. Methods In the OPT-BIRISK study, 7,758 ACS patients with both high ischemic and bleeding risks who completed 9-12 months DAPT after DES implantation were randomized to receive clopidogrel monotherapy or clopidogrel plus aspirin for 9 months. The primary endpoint was Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding at 9 months. Primary and key secondary endpoints included Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding and major adverse cardiovascular and cerebrovascular events (MACCE), respectively. Results Clopidogrel monotherapy demonstrated a consistent 25% non-significant reduction in BARC 2, 3, or 5 bleeding risk across troponin strata (troponin-negative: 2.8% vs. 3.7%, HR 0.75, 95% CI 0.54 - 1.06, P = 0.101; troponin-positive: 2.0% vs. 2.7%, HR 0.75, 95% CI 0.49 - 1.15, P = 0.181). Any bleeding risk was significantly lower with monotherapy in both subgroups (troponin-negative: 16.3% vs. 20.3%, HR 0.79, 95% CI 0.68-0.91, P = 0.001; troponin-positive: 12.4% vs. 15.5%, HR 0.79, 95% CI 0.66-0.94, P = 0.008). MACCE rates were comparable between treatment arms (troponin-negative: 2.3% vs. 3.2%, HR 0.70, 95% CI 0.48 - 1.01, P = 0.060; troponin-positive: 3.0% vs. 3.8%, HR 0.78, 95% CI 0.55 - 1.12, P = 0.175). No significant interaction was observed for all endpoints. Conclusions In bi-risk ACS patients completing 9-12 months of DAPT post-DES, extended clopidogrel monotherapy was associated with a lower risk of any bleeding without increasing the risk of MACCE compared to DAPT, irrespective of troponin status.