Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients With Acute Coronary Syndrome A Randomized Clinical Trial

IMPORTANCE Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis. OBJECTIVE To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea. INTERVENTIONS Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n = 149) or matched placebo (n = 151) for 24 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE. RESULTS Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1(interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81(53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% Cl, 0.49-0.96; P = .03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% Cl, 0.51-1.33; P = .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% Cl, 0.41-1.52; P = .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% Cl, 0.27-0.96; P = .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% Cl, 0.33-1.04; P = .07). CONCLUSIONS AND RELEVANCE Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings.