Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients.

Abstract

The effect of clopidogrel monotherapy as compared with extended dual antiplatelet therapy (DAPT) with clopidogrel and aspirin beyond 12 months after implantation of a drug-eluting stent remains uncertain in patients at high risk for recurrent ischemic events. In this open-label noninferiority trial conducted in South Korea, we enrolled patients with high-risk clinical or lesion characteristics in whom a drug-eluting stent had been implanted 12 months earlier and randomly assigned them, in a 1:1 ratio, to receive clopidogrel monotherapy or extended DAPT (clopidogrel plus aspirin). The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (noninferiority margin, 2.3 percentage points). Key secondary ischemic and bleeding end points were tested in a prespecified hierarchical order. Of the 3203 patients who underwent randomization, 1601 were assigned to receive clopidogrel monotherapy and 1602 to receive extended DAPT. Over the course of 24 months, a primary end-point event occurred in 80 patients (5.0%) in the monotherapy group and in 81 (5.1%) in the DAPT group (risk difference, -0.1 percentage points; 90% confidence interval [CI], -1.3 to 1.2; P = 0.001 for noninferiority). Death from any cause, myocardial infarction, stent thrombosis, or stroke (the key secondary ischemic end point) occurred in 60 patients (3.7%) in the monotherapy group and in 26 (1.6%) in the DAPT group (hazard ratio, 2.33; 95% CI, 1.47 to 3.69; P<0.001). BARC type 2, 3, or 5 bleeding (the key secondary bleeding end point) occurred in 28 patients (1.8%) in the monotherapy group and in 65 (4.1%) in the DAPT group (hazard ratio, 0.43; 95% CI, 0.27 to 0.67; P<0.001). The incidence of serious adverse events was similar in the two groups. Among patients at high risk for ischemic events 12 months after drug-eluting stent implantation, clopidogrel monotherapy was noninferior to extended DAPT with respect to net adverse clinical events at 24 months. (Funded by Chong Kun Dang and Samjin; A-CLOSE ClinicalTrials.gov number, NCT03947229.).