Effect of long-term adherence to clopidogrel on the VASP-PRI after elective coronary stent implantation: a randomized controlled study.

Abstract

The biological response to clopidogrel is highly variable and a poor responsiveness is associated with major adverse cardiac events. Adherence to therapy is a major cause of poor responsiveness but its impact on long-term platelet inhibition is unknown. The objective of the present study was to evaluate the effect of different programmes monitoring adherence to clopidogrel on platelet reactivity. The study took the form of a monocentric, parallel group, randomized controlled trial. Adults treated with clopidogrel 75mg after elective coronary stenting were randomized into one of three groups: (i) a standard of care group; (ii) a standard of care+adherence electronic monitoring group, in which drug intake was recorded but kept blinded until the study end; or (iii) an integrated care group, with regular feedback on recorded adherence. Clopidogrel response was assessed with the vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) at randomization, 3months and 6months. A total of 123 adults were enrolled and randomized. Baseline VASP-PRI was highly variable, with a mean of 48±18.8%. No difference between groups in VASP-PRI was found at 6months (P = 0.761), despite better adherence to clopidogrel in the integrated care group. However, adherence (P = 0.035) and baseline VASP-PRI (P = 0.015) were associated with VASP-PRI at 3months and 6months. The association between adherence and VASP-PRI was lost in patients with baseline VASP-PRI > 50%. Diabetes, CYP2C19*2 carrier status and body mass index were significant predictors of VASP-PRI. The platelet response to clopidogrel during chronic therapy remained highly variable, despite high adherence. Different adherence monitoring programmes did not affect VASP-PRI at 6months. Poor adherence is associated with lower VASP-PRI only in initial good responders to clopidogrel.