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.

Conflict of interest statement

Conflict of interest disclosures: All authors received salary support through an NHLBI research grant. Dr. Redford B. Williams reports holding a U.S. patent on the 5HTTLPR L allele for use as a marker of increased cardiovascular risk in stressed persons and is a founder and major stockholder of Williams LifeSkills, Inc. Dr. Becker reports receiving research grant support from Baxter, Bristol-Myers Squibb, Johnson & Johnson, and Regado Biosciences, and consulting/lecture fees from Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Regado Biosciences, and Sanofi-Aventis. Dr. Velazquez reports receiving research grants from Abbott Laboratories, Evalve, and Ikaria, and consulting fees from Boehringer Ingelheim, Gilead, and Novartis. Dr. Rogers reports receiving funding from Boston Scientific Corporation, HeartWare, and Thoratec Corporation. Dr. O’Connor reports receiving funding from Actelion Pharmaceuticals Ltd., Amgen, Inc., Biscardia LLC, Cardiology Consulting Associates, Faculty Connection, GE Healthcare, Ikaria, Neurotronik/Interventional Autonomics Corporation, Novella Clinical Inc., Pfizer Inc., Pozen, and Roche Diagnostics.

Figures

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