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Personalized Antiplatelet Therapy: The Odyssey Continues

We appreciate the interest of Dr. Bonello and colleagues in our paper on the RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt Thrombosis 3) study (1). However, all their comments and criticisms reveal a misunderstanding of the paper because all the points they raised were already discussed and clarified in the paper. First, the aim of the study was to test the hypothesis that nonresponsiveness to clopidogrel is a modifiable risk factor and not the comparison of prasugrel with clopidogrel, and ethical issues make unlikely the possibility to perform a randomized study using clopidogrel in the control arm in clopidogrel nonresponders. Second, in the RECLOSE-2 study, as well as in the GRAVITAS (Gauging Responsiveness with a VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety) trial, tailored therapy with an increased dose of clopidogrel in clopidogrel nonresponders had some effect on in vitro tests, but no clinical benefit (2,3). Thus, the historical cohort of the RECLOSE-2 trial may be used as the control arm. Third, the differences in baseline characteristics between the 2 patients groups were rigorously considered in the multivariable analyses. Fourth, the duration of prasugrel treatment, as well as the major and minor bleeding events, was clearly reported, with an increase in minor bleeding rate in prasugrel-treated patients, whereas no difference between groups was revealed in major bleeding, and the last finding supports the safety profile of prasugrel in clopidogrel nonresponders. Finally, the demonstration that high residual platelet reactivity on clopidogrel is a modifiable risk factor puts an end to what Dr. Bonello and colleagues define inappropriately as an odyssey.

• 2016 American College of Cardiology Foundation