Clopidogrel monotherapy in patients with and without on-treatment high platelet reactivity: a SMART-CHOICE substudy.

BACKGROUND

Although P2Y12 inhibitor monotherapy has emerged as a promising alternative for dual antiplatelet therapy (DAPT), there remains concern regarding the 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, three-month DAPT followed by P2Y12 inhibitor monotherapy was compared with 12-month DAPT in patients undergoing percutaneous coronary intervention. A 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). The 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.

CLINICAL TRIAL REGISTRATION: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy After DES (SMART-CHOICE) (ClinicalTrials.gov: NCT02079194).