PracticeUpdate: Cardiology - Winter 2018

EDITOR’S PICKS 9

Escitalopram vs Placebo Treatment for Depression Improves Long-Term Cardiac Outcomes in Patients With Acute Coronary Syndrome JAMA: The Journal of the American Medical Association

Take-home message • Patients with depression following recent acute coronary syndrome (ACS) were randomized to receive escitalopram (n=149) or placebo (n=151) for 24 weeks to evaluate the effect on long-term major adverse cardiac events (MACE). After a median of 8.1 years of follow-up, MACE occurred in 40.9% of the escitalopram group vs 53.6% of the placebo group (P = .03). • Treatment of post-ACS depression with escitalopram is associated with a lower risk of MACE vs treatment with placebo. Further studies are needed to confirm these findings. " …these new data support the general recommendation that treating depression in cardiac patients is important. " Abstract IMPORTANCE Depression has been associated with poorer medical outcomes in acute coro- nary 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 escit- alopram 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 ChonnamNational University Hospital, Gwangju, South Korea. INTERVENTIONS Patients were randomly assigned to receive either escitalopram in flexible dos- ages of 5, 10, 15, or 20 mg/d (n= 149) or matched placebo (n= 151) for 24 weeks. MAIN OUTCOMES AND MEASURES The primary out- come 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% com- pleted 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% CI, 0.49-0.96; P= .03). Compar- ing 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% CI, 0.51-1.33; P= .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, In this recent clinical trial among patients with ACS, a 24-month treatment with the antidepressant escitalopram was associ- ated with a 31% reduction in the primary endpoint of major adverse cardiovascular events (a composite of all-cause mortal- ity, cardiac death, MI, and PCI) after a COMMENT By Viola Vaccarino MD, PhD D epression is a common comorbid- ity in patients with coronary heart disease, and a known adverse prognostic indicator. It has been 15 years since the publication of the landmark NIH- funded Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial, which failed to demonstrate that treating depression in patients with acute coro- nary syndromes (ACS) would improve their clinical outcomes. These results were met with shocking disbelief from the behavioral cardiology research and practice community. Since then, several small and medium-sized clinical trials have continued to demonstrate that phar- macological and behavioral approaches to depression treatment are moder- ately effective in reducing the burden of depression and improving the quality of life of cardiac patients. However, whether treatment of depression also improves their cardiovascular morbidity and mor- tality has not been demonstrated.

median follow-up of 8.1 years. Although these results support the notion that treat- ing depression in ACS patients favorably influences their clinical outcomes, they need further confirmation. This study was based on a relatively small sample from a single center in Korea, where patient characteristics and treatment modalities may differ from other settings. In the US, previous studies of depression treatment on long-term clinical cardiovascular end- points in ACS patients have been negative thus far, although they were also limited in sample size. Thus, althoughmore research is needed, these new data support the general recommendation that treating depression in cardiac patients is important, as it can improve patients’ psychologi- cal well-being, quality of life, medication adherence, healthy lifestyle, and possibly, long-term clinical outcomes.

Dr. Vaccarino is the Wilton Looney Chair of Cardiovascular Research, and Professor and Chair of the Department of Epidemiology at the Rollins School of Public Health, Emory University in Atlanta,

Georgia. She holds a joint appointment at the Emory School of Medicine, Department of Medicine, Division of Cardiology.

0.41-1.52; P= .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P= .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 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. Effect of Escitalopram vs Placebo Treatment for Depression on Long-Term Cardiac Outcomes in Patients With Acute Coronary Syndrome: A Randomized Clinical Trial. JAMA 2018 Jul 24;320(4)350-358, JM Kim, R Stewart, YS Lee, et al. www.practiceupdate.com/c/71435

VOL. 3 • NO. 3 • 2018