Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events - The Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) platelet substudy

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 (n = 28) or placebo ( n = 36). Anticoagulants, aspirin, and ADP- receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), 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 betaTG ( P = 0.03) at weeks 6 and 16 and for P-selectin ( P = 0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period. Conclusions - Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.