Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial

Abstract

Importance: Mental stress can induce myocardial ischemia and also has been implicated in triggering cardiac events. However, pharmacological interventions aimed at reducing mental stress-induced myocardial ischemia (MSIMI) have not been well studied.

Objective: To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters.

Design, setting, and participants: The REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) study, a randomized, double-blind, placebo-controlled trial of patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 24, 2007, through August 24, 2011, at a tertiary medical center.

Interventions: 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.

Main outcomes and measures: Occurrence of MSIMI, defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in 2 or more leads, lasting for 3 or more consecutive beats, during 1 or more of 3 mental stressor tasks.

Results: Of 127 participants randomized to receive escitalopram (n = 64) or placebo (n = 63), 112 (88.2%) completed end point assessments (n = 56 in each group). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4%-43.0%]) had absence of MSIMI during the 3 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 = .56).

Conclusions and relevance: Among patients with stable coronary heart disease and baseline MSIMI, 6 weeks of escitalopram, compared with placebo, resulted in a lower rate of MSIMI. There was no statistically significant difference in exercise-induced ischemia. Replication of these results in multicenter settings and investigations of other medications for reducing MSIMI are needed.

Trial registration: clinicaltrials.gov Identifier: NCT00574847.

Figure 1

Study flow for REMIT Trial. *Reasons given for patients not consented to REMIT (n=2294): Lack of interest (n=529); living too far away (n=75); lack of approval of primary clinical provider or study PI because of medical comorbidities (n=457); other (wrong contact information, coumadin) (n=127); awaiting phone screening (n=239); currently taking antidepressants that could not be discontinued (n=91); would contact later due to recent procedures or patient preference (n=127); awaiting approval of primary clinical providers (n=322); attempted but failed to contact (left message and/or no answer, etc.) (n=327). †Reasons for patients who provided consent but did not proceed with baseline assessments: taking antidepressant that could not be discontinued (n=5); safety concern of primary cardiologists (n=2); Beck Depression Inventory score <4 (initial exclusion criteria that was eliminated rapidly via IRB approval) (n=11); dropped out due to medical conditions (n=7); family-related issues (n=8); changed mind about the study medication or job changes (n=11); and no reason provided (n=21). ‡Two patients randomized to escitalopram declined to take study medication; 5 patients randomized to placebo did not take study medication.