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

Victor L. Serebruany, Alexander H. Glassman, Alex I. Malinin, Charles Nemeroff, Dominique Musselman, Louis T. Van Zyl, Mitchell S. Finkel, K. Ranga R Krishnan, Michael Gaffney, Wilma Harrison, Robert M. Califf, Christopher M. O'Connor

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)939-944
Number of pages6
JournalCirculation
Volume108
Issue number8
DOIs
StatePublished - Aug 26 2003
Externally publishedYes

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Sertraline
Serotonin Uptake Inhibitors
Antidepressive Agents
Blood Platelets
Biomarkers
Myocardial Infarction
Acute Coronary Syndrome
Placebos
P-Selectin
E-Selectin
clopidogrel
Platelet Activation
Aspirin
CD31 Antigens
Purinergic P2 Receptors
Platelet Factor 4
Therapeutics
Cerebrovascular Disorders
Thromboxane B2
Vascular Cell Adhesion Molecule-1

Keywords

  • Antidepressants
  • Coronary disease
  • Depression
  • Platelets
  • Trials

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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. / Serebruany, Victor L.; Glassman, Alexander H.; Malinin, Alex I.; Nemeroff, Charles; Musselman, Dominique; Van Zyl, Louis T.; Finkel, Mitchell S.; Krishnan, K. Ranga R; Gaffney, Michael; Harrison, Wilma; Califf, Robert M.; O'Connor, Christopher M.

In: Circulation, Vol. 108, No. 8, 26.08.2003, p. 939-944.

Research output: Contribution to journalArticle

Serebruany, Victor L. ; Glassman, Alexander H. ; Malinin, Alex I. ; Nemeroff, Charles ; Musselman, Dominique ; Van Zyl, Louis T. ; Finkel, Mitchell S. ; Krishnan, K. Ranga R ; Gaffney, Michael ; Harrison, Wilma ; Califf, Robert M. ; O'Connor, Christopher M. / 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. In: Circulation. 2003 ; Vol. 108, No. 8. pp. 939-944.
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abstract = "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.",
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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

AU - Musselman, Dominique

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.

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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.

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KW - Coronary disease

KW - Depression

KW - Platelets

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