Risk of Bleeding in Patients on Full-Dose Enoxaparin With Venous Thromboembolism and Selective Serotonin Reuptake Inhibitors

Background: Selective serotonin reuptake inhibitors (SSRIs) are very commonly prescribed agents that are also potent antiplatelet agents. Objective: This study was designed compare the rate of major bleeding events between patients who were treated with low-molecular-weight heparin (LMWH) for venous thromboembolism (VTE) on SSRIs and those not on chronic SSRI therapy. Methods: This was a retrospective cohort study of 575 patients with a primary or secondary diagnosis of an acute VTE initiated on full-dose enoxaparin with or without an SSRI between October 1, 2009, and October 1, 2014, in a 443-bed, single tertiary care referral county teaching hospital. Results: No significant difference was found in the incidence of major bleeding in the SSRI versus non-SSRI group (19.6% vs 17.0%, P = 0.548). Ad hoc analysis demonstrated an elevated risk of major bleeding in patients on escitalopram compared with those on any of the other SSRIs (46.2% vs 15.2%, P = 0.018). Multivariate analysis demonstrated that escitalopram use—OR (95% CI) = 18.85 (1.84-193.6)—was associated with increased major bleeding, and acid suppressive therapy—0.24 (0.07-0.90); P = 0.014—was associated with decreased major bleeding in patients reporting alcohol use. Conclusion: No difference was found in the incidence of major bleeding in patients on LMWH and SSRIs versus those on LMWH but not on SSRIs. However, ad hoc findings showed a significantly higher rate of major bleeding events in patients who received escitalopram and alcohol among patients on full-dose enoxaparin for VTE. These findings merit further exploration.