Individuals receiving clopidogrel exhibit a wide variability in response that follows a normal distribution. The clinical implications of this variability are unknown but potentially are important. Clinical trials are needed to define whether hyporesponders to clopidogrel are at increased risk for thrombotic events and whether hyper-responders are at increased risk for bleeding. If so, the individualization of antiplatelet therapy, including clopidogrel dosing, may be possible in the future but will require the ability to easily and reproducibly measure responsiveness by a method that has been proven to be predictive of clinical events.

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Background-Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity.Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). Methods and Results-Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (nϭ28) or placebo (nϭ36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, ␤-thromboglobulin (␤TG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B 2 , 6-ketoprostaglandin F 1a , vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for ␤TG (Pϭ0.03) at weeks 6 and 16 and for P-selectin (Pϭ0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and ␤TG concentrations across the entire treatment period. Conclusions-Treatment