Major Adverse Cardiovascular Events in Antidepressant Users within Patients with Ischemic Heart Diseases: A Nationwide Cohort Study

Background To evaluate the effect of antidepressants on the development of major adverse cardiovascular events (MACEs) in patients with ischemic heart disease (IHD), we analyzed the association between antidepressant use and the risk of MACE development. Methods Patients with depression and a history of IHD between 2008 and 2012 were identified by using the National Health Insurance Service database. A cohort was followed up for the development of MACE until the end of 2015. Hazard ratios (HRs) for myocardial infarction, stroke, and cardiovascular death were estimated by Cox proportional hazard regression in a propensity score-matched cohort. Results Over a median 4.2 years of follow-up, 2943 MACE occurred in 18,981 antidepressant users. Use of antidepressants was not associated with the incidence of MACE when compared with antidepressant nonusers (adjusted HR, 1.00; 95% confidence interval, 0.95-1.05). Among the analyses according to different classes of antidepressants, the increased risk of stroke was only observed in the subgroup of selective serotonin reuptake inhibitor (SSRI) users. Dose-response findings reported greater risk in those with higher doses of use (SSRIs with ≥1.0 defined daily dose; adjusted HR, 1.14; 95% confidence interval, 1.06-1.23), whereas duration response does not support association. Conclusions Compared with antidepressant nonusers, use of antidepressants was not associated with occurrence of MACEs in patients with depression and IHD. Although the overall effect of antidepressants on the risk of MACE was neutral, careful monitoring of MACE development is recommended in high-dose SSRI users.