TY - JOUR
T1 - Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events
T2 - The Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) platelet substudy
AU - Serebruany, Victor L.
AU - Glassman, Alexander H.
AU - Malinin, Alex I.
AU - Nemeroff, Charles B.
AU - Musselman, Dominique L.
AU - Van Zyl, Louis T.
AU - Finkel, Mitchell S.
AU - Krishnan, K. Ranga R
AU - Gaffney, Michael
AU - Harrison, Wilma
AU - Califf, Robert M.
AU - O'Connor, Christopher M.
PY - 2003/8/26
Y1 - 2003/8/26
N2 - 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, β -thromboglobulin (βTG), 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 βTG (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 βTG 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.
AB - 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, β -thromboglobulin (βTG), 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 βTG (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 βTG 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.
KW - Antidepressants
KW - Coronary disease
KW - Depression
KW - Platelets
KW - Trials
UR - http://www.scopus.com/inward/record.url?scp=0043180436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0043180436&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000085163.21752.0A
DO - 10.1161/01.CIR.0000085163.21752.0A
M3 - Article
C2 - 12912814
AN - SCOPUS:0043180436
VL - 108
SP - 939
EP - 944
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 8
ER -