SSRI Given for Post-ACS Depression May Cut Cardiac Event Risk

Marlene Busko

July 27, 2018

Patients with a recent hospitalization for acute coronary syndrome (ACS) found to have clinical depression may gain some protection from future cardiac events by starting therapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram, a small study suggests.

Such patients with acute myocardial infarction (MI) or unstable angina within the past 2 weeks who received the antidepressant for about 6 months in the randomized, placebo-controlled trial showed a significantly reduced risk for a major adverse cardiac event (MACE) during a median 8-year follow-up (mean, 8.4 years). 

The benefit appeared to be driven predominantly by a significantly reduced risk for acute MI during the prespecified long-term follow-up of the Escitalopram for Depression in Acute Coronary Syndrome (EsDEPACS) cohort.

The analysis was published July 24 in JAMA with first author Jae-Min Kim, MD, PhD, National University Medical School, Gwangju, South Korea.

"There have been few data showing the beneficial effects of antidepressants on long-term cardiac outcomes," Kim told | Medscape Cardiology in an email.

"Our study is the first to report the association in a randomized placebo-controlled design," he added, "and therefore could serve as a basis for a new treatment guideline for these patients."

The authors acknowledge some limitations of the analysis, including that it was based on a Korean population at a single center and didn't account for ACS severity.

Also, randomized therapy lasted for 6 months, but "no attempt was made to investigate depression occurrence or antidepressant use after the 1-year follow-up, which could also affect long-term cardiac outcomes," the group writes.

"However, the number of participants using any antidepressant was small at 1 year after ACS, and principal findings were not changed substantially after excluding this group."

Still, observed Kim, the study could offer evidence that screening for and treating depression in patients with a recent heart attack is "good clinical practice."

The researchers used the Beck Depression Inventory to screen patients with ACS within the past 2 weeks at their center from 2007 to 2013; the depression screening test was repeated every 3 months. Patients with a score greater than 10 at any time were evaluated by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI) for diagnosis of major or minor depression.

They randomly assigned 300 such patients found to have clinical depression at baseline to receive escitalopram or placebo for 24 weeks in addition to other appropriate therapies. Major depression had been identified in 55% of the group.

The assigned treatment was given initially at 10 mg/day, a dosage that could be reduced to 5 mg/day or increased to up to 20 mg/day according to patient response and tolerance. Mean dosages at the last visit were 7.6 mg/day for escitalopram and 8.5 mg/day for placebo.

Escitalopram was superior to placebo in reducing depressive symptoms at 24 weeks; serious adverse events (including suicide) were rare, Kim said.

After a median follow-up of 8.1 years, the rate of incident MACE (all-cause mortality, MI, or percutaneous coronary intervention) was significantly reduced in the escitalopram group compared with the placebo group, 40.9% vs 53.6%, respectively, for a hazard ratio (HR) of 0.69 (95% confidence interval [CI], 0.49 - 0.96; P = .03).

As for the secondary endpoints making up the composite primary endpoint, MI risk was significantly reduced in the active-therapy group, for an HR of 0.54 (95% CI, 0.27 - 0.96, P = .04). However, there were no significant differences for the other endpoint components.

Some studies have suggested that antidepressants confer independent cardiovascular protection. In addition, biological mechanisms could plausibly explain a long-term cardioprotective effect of SSRI therapy in patients with depression and a history of ACS, Kim said.

For example, as the report notes, "escitalopram may positively affect common mediators of ACS and depression, including brain-derived neurotrophic factor and proinflammatory cytokines, and may normalize autonomic and platelet dysfunction, which have adverse effects on cardiac outcomes."

There is also evidence that SSRIs may adversely heighten the effects of antiplatelet agents in secondary prevention patients taking both kinds of agents.

Kim reported no conflicts; disclosures for the other authors are in the report.

JAMA. 2018;320:350-358. Abstract

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