Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia: Results of the REMIT Trial

Study Questions:

What is the effect of 6 weeks of escitalopram treatment versus placebo on mental stress–induced myocardial ischemia (MSIMI) and other psychological stress–related biophysiological and emotional parameters?

Methods:

The REMIT study (Responses of Mental Stress–Induced Myocardial Ischemia to Escitalopram Treatment) is a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease (CHD) and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center. Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg/d, with titration to 20 mg/d in 3 weeks) or placebo over 6 weeks. Occurrence of MSIMI was defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or electrocardiogram evidence for ischemia during one or more of three mental stressor tasks.

Results:

Mean age was 64 years, 100% were white, 20% were women, and the frequency of use of evidence-based coronary heart disease treatments was comparable to most studies. Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed endpoint assessments. After 6 weeks, more patients taking escitalopram (34.2%; 95% confidence interval [CI], 25.4%-43.0%) had absence of MSIMI during the three mental stressor tasks compared with patients taking placebo (17.5%; 95% CI, 10.4%-24.5%), based on the unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (odds ratio, 2.62; 95% CI, 1.06-6.44). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8%; 95% CI, 36.6%-55.0%) than in patients receiving placebo (52.5%; 95% CI, 43.3%-61.8%), but this difference was not statistically significant (adjusted odds ratio, 1.24; 95% CI, 0.60-2.58; p = 0.56).

Conclusions:

The authors concluded that among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI.

Perspective:

Studies have shown that documentation of mental stress–induced ischemia is at least as predictive of cardiovascular events as exercise-induced ischemia. The results are very interesting and biologically plausible. As suggested by the authors, replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Stress

Keywords: Urinary Bladder Neoplasms, Coronary Artery Disease, Intention, Myocardial Ischemia, Depressive Disorder, Major, Sodium, Heart Failure, Stroke Volume, Electrocardiography, Ions, Stress, Psychological


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