Association between SSRI use and cardiovascular outcomes in patients with coronary artery disease and generalized anxiety disorder: A real-world cohort study

Abstract

Background and aims: Coronary artery disease (CAD) is a leading cause of cardiovascular mortality, and generalized anxiety disorder (GAD) is highly prevalent among CAD patients, worsening cardiovascular outcomes. While selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for anxiety disorders, their impact on cardiovascular prognosis in patients with CAD and GAD remains unclear.

Methods: This retrospective cohort study utilized real-world data from the TriNetX database. Patients diagnosed with both CAD and GAD between 2016 and 2025 were included and categorized into SSRI users and non-users. Propensity score matching (PSM) was applied to balance baseline characteristics. The primary outcome was major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and all-cause mortality. Secondary outcomes included individual MACE components and all-cause hospitalization. Hazard ratios (HRs) were estimated using Cox proportional hazards models.

Results: After 1:1 PSM, 54,526 SSRIs users and 54,526 non-users were analyzed. SSRIs use was significantly associated with a lower one-year risk of MACE (HR: 0.77, 95 % CI: 0.74-0.81, p < 0.001). Similar protective effects were observed across secondary outcomes and subgroups, such as diabetes mellitus, obesity, dyslipidemia, and nicotine dependence. Landmark analyses confirmed consistent results. Negative control analyses showed no significant differences, minimizing bias.

Conclusion: SSRIs use is associated with a lower one-year MACE rate in patients with CAD and GAD. These findings highlight the potential cardiovascular benefits of SSRIs in this population. Further clinical trials are warranted to validate these results and explore long-term effects.

Keywords: CAD; GAD; MACE; SSRI.