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Cited by 103Cardiac Health and Mental HealthCardiac Imaging and DiagnosticsHeart Rate Variability and Autonomic Control

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

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Jiang, Wei, Velazquez, Eric J., Kuchibhatla, Maragatha, Samad, Zainab, Boyle, Stephen H., Kuhn, Cynthia, Becker, Richard C., Ortel, Thomas L. +3 more·2013·JAMA
DOI 10.1001/jama.2013.5566PMC PMC4378823
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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.

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  • Other controlled trials have demonstrated modest improvements associated with SSRIs in patients with heart disease on surrogate markers, including heart rate variability and mental stress-induced myocardial ischemia, although other studies have found no such effect on clinical events or other markers.

    “Other controlled trials have demonstrated modest improvements associated with SSRIs in patients with heart disease on surrogate markers, including heart rate variability 179 and mental stress-induced myocardial ischemia, 180 although other studies have found no such effect on clinical events or other markers. 179,181”

    From Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association (2021) · cites this paper as [180]

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Authors
Jiang, W., Velazquez, E. J., Kuchibhatla, M., Samad, Z., Boyle, S. H., Kuhn, C., Becker, R. C., Ortel, T. L., Williams, R. B., Rogers, J. G., & O’Connor, C.
Affiliations
Duke Medical Center (US)
Corresponding author
Jiang, Wei
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2013-05-22
Volume
309
Issue
20
Pages
2139
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2013.5566
PMC
PMC4378823
OpenAlex
W2060231842
Cited by
103
References
2
Citations by year
2026: 5 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 11 · 2016: 10 · 2015: 5 · 2014: 15 · 2013: 7
FWCI
8.39
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (P30AG028716)
  • National Heart, Lung, and Blood Institute (P01HL036587, R01HL118077, R01HL085704)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
escitalopram, mental stress-induced myocardial ischemia, coronary artery disease, selective serotonin reuptake inhibitors, psychological stress, ST-segment depression, exercise-induced ischemia, regional wall motion abnormalities, left ventricular ejection fraction, intention-to-treat analysis, multiple imputation
MeSH terms
Aged, Coronary Disease, Double-Blind Method, Electrocardiography, Emotions, Female, Humans, Male, Middle Aged, Stress, Psychological, Citalopram, Exercise, Ventricular Function, Left, Myocardial Ischemia, Selective Serotonin Reuptake Inhibitors, Disease Progression

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