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

Abstract

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).

Conflict of interest statement

J.Y. Hahn has received grants from Abbott Vascular, Biotronik, Boston Scientific, Daiichi Sankyo, and Medtronic, and speaker’s fees from AstraZeneca, Daiichi Sankyo, and Sanofi-Aventis. H.C. Gwon has received research grants from Abbott Vascular, Boston Scientific, and Medtronic, and speaker’s fees from Abbott Vascular, Boston Scientific, and Medtronic. The other authors have no conflicts of interest to declare.

Figures

Figure 1

Study flow. DAPT: dual antiplatelet therapy; HPR: high platelet reactivity; PRU: platelet reactivity unit

Central illustration

Comparison of 12-month MACCE rate according to on-treatment PRU level and type of P2Y12 inhibitor. The cumulative incidence of MACCE at 12 months was compared according to HPR among patients receiving clopidogrel. It was also compared to those who received potent P2Y12 inhibitor monotherapy. The incidence of 12-month MACCE was significantly higher in patients with HPR than in other groups. HPR: high platelet reactivity; MACCE: major adverse cardiovascular and cerebrovascular events; PRU: platelet reactivity unit

Figure 2

Comparison of 12-month MACCE rate according to HPR on clopidogrel. The cumulative incidence of MACCE at 12 months was compared between the long-term DAPT and monotherapy groups for those (A) with HPR (>275) or (B) without HPR (≤275) among patients on clopidogrel. * Multivariable analysis after adjusting for age and sex. CI: confidence interval; DAPT: dual antiplatelet therapy; HPR: high platelet reactivity; HR: hazard ratio; PRU: platelet reactivity unit

Figure 3

Comparison of 12-month BARC 2-5 bleeding rate according to HPR on clopidogrel. The cumulative incidence of BARC 2-5 bleeding at 12 months was compared between the long-term DAPT and monotherapy groups for those (A) with HPR (>275) or (B) without HPR (≤275) among patients on clopidogrel. * Multivariable analysis after adjusting for age and sex. BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; HPR: high platelet reactivity; HR: hazard ratio; PRU: platelet reactivity unit