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

Abstract

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.