Selective serotonin reuptake inhibitors yield additional antiplatelet protection in patients with congestive heart failure treated with antecedent aspirin

Abstract

Clinical depression has been identified as an independent risk factor for increased mortality in patients with coronary artery disease. Enhanced platelet activity has been suggested as the mechanism responsible for this adverse association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelets in patients undergoing coronary stenting. We sought to determine whether concomitant therapy with SSRIs would yield additional anti-platelet benefit in patients with congestive heart failure (CHF) already treated with antecedent aspirin. A total of 88 patients with left ventricular ejection fraction (LVEF) -40% or CHF symptoms in the setting of preserved systolic function and NYHA Class II-IV were analyzed. Of these, 23 patients (26%) were chronic SSRI users (SSRIq), and 65 patients were free from SSRI therapy (SSRIy). All patients received aspirin (325 mg) for at least 1 month prior to platelet studies. Platelets were assessed by aggregometry, flow cytometry and a rapid analyzer. The SSRIq group exhibited a substantial decrease in platelet activity when compared with SSRIy patients, as manifested by a significant reduction in ADP-(Ps0.001), and collagen-induced (Ps0.02) aggregation, and the expression of PECAM-1 (Ps0.03), GPIb (Ps0.03), GP IIbyIIIa antigen (Ps0.02) and GP IIbyIIIa activity with PAC-1 antibody (Ps0.04) and P-selectin (Ps0.02). Therapy with SSRIs also resulted in the reduced formation of platelet-leukocyte microparticles (Ps 0.01). Epinephrine-induced aggregation in plasma, collagen-induced whole blood aggregation, closure time and expression of vitronectin receptor, CD63, CD107a, CD107b and CD151 did not differ between groups. In patients with CHF already on aspirin, SSRI therapy was associated with further inhibition of platelet function. This observation may help to explain some of the clinical benefits associated with SSRI therapy. Further clinical trials may help to elucidate the potential outcome benefits of SSRIs in other potential thrombotic circumstances.

Interactions between integrin αIIbβ3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans

“…The decrease in platelet aggregation in SERT-null mice is reminiscent of the diminished 5-HT content found in subjects chronically exposed to SSRIs (35) and the reduced platelet activation observed in depressed patients after chronic SSRI treatment (36). Additionally, short-term, open-label treatment of depressed patients with the SSRI paroxetine leads to a significant reduction in the number of functional αIIbβ3 and plasma concentrations of proaggregatory factors (37).…”

Depressive Affect and Hospitalization Risk in Incident Hemodialysis Patients

“…In addition to nonadherence and other behavioral components (alcohol, smoking, decreased physical activity) linked to depression, biologic mechanisms linking depression to coronary artery disease have been proposed (25). Abnormal platelet function and reactivity are more prevalent in depressed patients (26), which may be mediated through serotonin imbalance (27). Dysregulation of the hypothalmic-pituitary-adrenal axis in depressed states may also play a role, particularly with regard to effect on stress responses, either biochemically with inflammatory cytokine imbalances or clinically through abnormalities of BP and heart rate (28)(29)(30).…”

Serotonin Reuptake Inhibitors and Cardiovascular Disease

“…Data have accumulated indicating that depression is associated with platelet activation and that the SSRIs [1,85,86] affect platelet function. SSRIs reduce platelet activity in patients on aspirin therapy and in patients with heart failure [87]. Platelet activity is also decreased by in vitro exposure to both sertraline (an SSRI) and N-desmethylsertraline, the nonactive metabolite of sertraline [88].…”