Comparison of clopidogrel monotherapy versus prolonged DAPT based on the GRACE risk score in patients with acute coronary syndromes at high ischemic and bleeding risk: a subgroup analysis of the OPT-BIRISK randomized clinical trial

OBJECTIVE: This study assessed the effect of clopidogrel monotherapy versus extended Dual antiplatelet therapy (DAPT) on outcomes in patients with acute coronary syndromes (ACS) who have completed 9-12 months of DAPT after Percutaneous Coronary Intervention (PCI) and meet both high bleeding and high ischemia risk (birisk), stratified by Global Registry of Acute Coronary Events (GRACE) risk score. METHODS: In the OPT-BIRISK study, 7758 ACS Patients who completed 9-12 months of DAPT after PCI were randomized either to clopidogrel monotherapy or extended DAPT. This prespecified subgroup analysis categorized patients by GRACE score into intermediate-high-risk (>88) and low-risk (≤88) groups. The primary endpoint of the study was BARC 2, 3, or 5 bleeding. The key secondary endpoint was the rate of major adverse cardio-cerebral events (MACCE; the composite of all-cause death, myocardial infarction, stroke or clinically driven revascularization). FINDINGS: In low-risk patients, BARC 2, 3, or 5 bleeding occurred in 49 (2.7 %) with clopidogrel monotherapy versus 69 (3.6 %) with extended DAPT (HR 0.73, 95 % CI 0.50-1.05; p = 0.088).In intermediate-high-risk patients, clopidogrel monotherapy versus extended DAPT showed comparable BARC 2, 3, or 5 bleeding (2.3 % vs. 3.0 %; HR 0.77, 95 % CI 0.52-1.14; p = 0.8377), but significantly reduced MACCE (2.9 % vs. 4.1 %; HR 0.69, 95 % CI 0.49-0.97; p = 0.0332). In the overall trial population, there was no significant interaction between the GRACE score and treatment group for the primary or key secondary endpoints (P > 0.05 for all outcomes). CONCLUSIONS: Among birisk patients with ACS, clopidogrel monotherapy was associated with lower incidence of all bleeding events (BARC 1-5) versus extended DAPT regardless of GRACE score, but showed no significant difference in BARC 2, 3, or 5 bleeding. Moreover, it was associated with lower MACCE incidence versus extended DAPT in intermediate-high-risk groups.