Clopidogrel Monotherapy in Patients with and without On-Treatment High Platelet Reactivity: a SMART-CHOICE sub-study.

Background Although P2Y12 inhibitor monotherapy has been emerged as a promising alternative for dual antiplatelet therapy (DAPT), there remains concern regarding safety of clopidogrel monotherapy. Aims We sought to investigate clinical outcomes of clopidogrel monotherapy in patients with and without on-treatment high platelet reactivity (HPR). Methods In the SMART-CHOICE study, 3-month DAPT followed by P2Y12 inhibitor monotherapy was compared with 12-month DAPT undergoing percutaneous coronary intervention. Of these, platelet function test was performed for 833 patients with clopidogrel-based therapy. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE: a composite of all-cause death, myocardial infarction, or stroke) at 12 months. Results Overall, 108 (13.0%) patients had HPR on clopidogrel. Patients with HPR had a significantly higher rate of MACCE than patients without HPR (8.7% vs 1.5%, adjusted HR 3.036, 95% CI 1.060-8.693, P=0.038). Treatment effect of clopidogrel monotherapy for the 12-month MACCE was not significantly different compared with DAPT among patients with HPR (8.0% vs. 9.4%, adjusted HR 0.718, 95% CI 0.189-2.737, P=0.628) and without HPR (2.2% vs. 0.9%, adjusted HR 2.587, 95% CI 0.684-9.779, P=0.161; adjusted P for interaction=0.170). Conclusions Clopidogrel monotherapy showed treatment effects comparable to DAPT for MACCE in patients with or without HPR. However, HPR was significantly associated with an increased risk of MACCE in clopidogrel-treated patients regardless of maintenance of aspirin.