Published online before print August 11, 2003, doi: 10.1161/01.CIR.0000085163.21752.0A
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(Circulation. 2003;108:939.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From the Sinai Center for Thrombosis Research (V.L.S., A.I.M.), Johns Hopkins University, Baltimore, Md; Columbia University (A.H.G.), New York, NY; Emory University (C.B.N., D.L.M), Atlanta, Ga; Queen’s University (L.T.v.Z.), Kingston, Ontario, Canada; West Virginia University (M.S.F.), Morgantown, WV; Duke Clinical Research Institute (K.R.R.K, R.M.C., C.M.O.), Durham, NC; and Pfizer, Inc (M.G., W.H.), New York, NY.
Reprint requests to Dr Victor L. Serebruany, Center for Thrombosis Research, Sinai Hospital of Baltimore, 2401 W Belvedere Ave, Schapiro Research Bldg–Room 202, Baltimore, MD 21215. E-mail Heartdrug{at}aol.com
Received February 18, 2003; revision received April 24, 2003; accepted April 25, 2003.
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, ß-thromboglobulin (ßTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, 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 ßTG (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 ßTG 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.
Key Words: depression • coronary disease • platelets • antidepressants • trials
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