Response to Letters Regarding Article, “Platelet Reactivity and Cardiovascular Outcomes After Percutaneous Coronary Intervention: A Time-Dependent Analysis of the Gauging Responsiveness With a VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) Trial”

Abstract

We thank Dr Nezami and colleagues for their interest in our study. As they note, statin therapy has been associated with improved clinical outcomes after percutaneous coronary intervention. Although an early observational study suggested an interaction between atorvastatin and the antiplatelet effect of clopidogrel in the acute phase of treatment, presumably due to shared metabolism via the CYP3A4 pathway, this does not occur during maintenance clopidogrel therapy and was not confirmed in subsequent randomized pharmacodynamic studies. In addition, clinical outcome studies have failed to identify a clear impact of statins on the ability of clopidogrel to reduce recurrent ischemic events.1 In order to address the questions of Dr Nezami and colleagues about our trial, we assessed the effect of statin use in GRAVITAS by incorporating this covariate into our time-dependent multivariate regression model.2 Statin use was not associated with clinical outcome at 60 days (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI], 0.27–3.02) or 6 months (adjusted HR 0.86. 95% CI, 0.39–1.91), nor did it affect the relationship between on-treatment reactivity <208 PRU and outcome at either time point (adjusted HR 0.23, 95% CI, 0.05–0.98, P =0.047 at 60 days and adjusted HR 0.54, 95% CI: 0.28–1.04, P …