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

ABSTRACT: 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.To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters.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.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, 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.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).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.clinicaltrials.gov Identifier: NCT00574847.

SUBMITTER: Jiang W

PROVIDER: S-EPMC4378823 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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

Jiang Wei W Velazquez Eric J EJ Kuchibhatla Maragatha M Samad Zainab Z Boyle Stephen H SH Kuhn Cynthia C Becker Richard C RC Ortel Thomas L TL Williams Redford B RB Rogers Joseph G JG O'Connor Christopher C

JAMA 20130501 20

<h4>Importance</h4>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.<h4>Objective</h4>To examine the effects of 6 weeks of escitalopram treatment vs placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters.<h4>Design, setting, and participants</h4>The REMIT (Responses o ...[more]

PMID: 23695483

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Project description:ImportancePosttraumatic stress disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear.ObjectiveTo evaluate the association of PTSD with mental stress-induced myocardial ischemia among individuals who survived a myocardial infarction (MI).Design, setting, and participantsThis cross-sectional study included 303 patients aged 18 to 60 years enrolled from a university-affiliated network. Participants had a verified history of MI within 8 months. Data were collected from June 2011 to March 2016, and data analysis was conducted from March to June 2019.ExposuresA clinical diagnosis of PTSD (lifetime and current) was obtained using the Structured Clinical Interview from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and PTSD symptom subscales were assessed with the civilian version of the PTSD Symptom Checklist.Main outcomes and measuresPatients received technetium 99m-labeled sestamibi myocardial perfusion imaging at rest, with mental stress (ie, a speech task) and conventional stress (ie, exercise or pharmacologic). A summed difference score (ie, the difference between stress and rest scores) was used to assess ischemia under both stress conditions.ResultsAmong 303 participants (148 [48.8%] women; 198 [65.3%] African American; mean [SD] age, 51 [7] years), the prevalence of PTSD was 14.5% (44 patients). Patients with PTSD had a higher rate of ischemia with mental stress than those without PTSD (12 of 44 [27.3%] vs 38 of 259 [14.7%]; P = .04) and more than twice the mean number of ischemic segments (1.2 [95% CI, 0.5-1.8] vs 0.5 [95% CI, 0.3-0.7]; P < .001), but there was no difference in conventional stress ischemia (10 of 44 [22.7%] vs 60 of 259 [23.2%]; P = .91). Increasing levels of PTSD symptoms were associated with higher odds of ischemia with mental stress (adjusted odds ratio [OR] per 5-point score increase, 1.18; 95% CI 1.04-1.35; P = .01) but not with conventional stress (adjusted OR per 5-point score increase, 1.05; 95% CI, 0.92-1.21; P = .47). Reexperiencing trauma was the symptom cluster most robustly associated with the presence of ischemia with mental stress (adjusted OR per 5-point score increase, 1.87; 95% CI 1.21-2.91; P = .005), followed by avoidance and numbing (adjusted OR per 5-point score increase, 1.51; 95% CI, 1.07-2.14; P = .02).Conclusions and relevanceIn this study of young and middle-aged individuals with MI, with a large representation of women and patients from racial/ethnic minority groups, PTSD was associated with the development of myocardial ischemia with mental stress. A higher ischemic response to mental stress represents a potential pathway associating PTSD with adverse outcomes after MI.

Project description:ImportanceMental stress-induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated.ObjectiveTo compare the association of mental stress-induced or conventional stress-induced ischemia with adverse cardiovascular events in patients with CHD.Design, setting, and participantsPooled analysis of 2 prospective cohort studies of patients with stable CHD from a university-based hospital network in Atlanta, Georgia: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 (last follow-up, February 2020).ExposuresProvocation of myocardial ischemia with a standardized mental stress test (public speaking task) and with a conventional (exercise or pharmacological) stress test, using single-photon emission computed tomography.Main outcomes and measuresThe primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure.ResultsOf the 918 patients in the total sample pool (mean age, 60 years; 34% women), 618 participated in MIPS and 300 in MIMS2. Of those, 147 patients (16%) had mental stress-induced ischemia, 281 (31%) conventional stress ischemia, and 96 (10%) had both. Over a 5-year median follow-up, the primary end point occurred in 156 participants. The pooled event rate was 6.9 per 100 patient-years among patients with and 2.6 per 100 patient-years among patients without mental stress-induced ischemia. The multivariable adjusted hazard ratio (HR) for patients with vs those without mental stress-induced ischemia was 2.5 (95% CI, 1.8-3.5). Compared with patients with no ischemia (event rate, 2.3 per 100 patient-years), patients with mental stress-induced ischemia alone had a significantly increased risk (event rate, 4.8 per 100 patient-years; HR, 2.0; 95% CI, 1.1-3.7) as did patients with both mental stress ischemia and conventional stress ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6). Patients with conventional stress ischemia alone did not have a significantly increased risk (event rate, 3.1 per 100 patient-years; HR, 1.4; 95% CI, 0.9-2.1). Patients with both mental stress ischemia and conventional stress ischemia had an elevated risk compared with patients with conventional stress ischemia alone (HR, 2.7; 95% CI, 1.7-4.3). The secondary end point occurred in 319 participants. The event rate was 12.6 per 100 patient-years for patients with and 5.6 per 100 patient-years for patients without mental stress-induced ischemia (adjusted HR, 2.0; 95% CI, 1.5-2.5).Conclusions and relevanceAmong patients with stable coronary heart disease, the presence of mental stress-induced ischemia, compared with no mental stress-induced ischemia, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction. Although these findings may provide insights into mechanisms of myocardial ischemia, further research is needed to assess whether testing for mental stress-induced ischemia has clinical value.

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

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

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