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).


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 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 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.
Serebruany
Victor L
VL
Sinai Center for Thrombosis Research, Johns Hopkins University, Baltimore, MD 21215, USA. Heartdrug@aol.com
Glassman
Alexander H
AH
Malinin
Alex I
AI
Nemeroff
Charles B
CB
Musselman
Dominique L
DL
van Zyl
Louis T
LT
Finkel
Mitchell S
MS
Krishnan
K Ranga R
KR
Gaffney
Michael
M
Harrison
Wilma
W
Califf
Robert M
RM
O'Connor
Christopher M
CM
D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood* / Q000150:complications; D003863:Depression / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D016896:Treatment Outcome
D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline