Responses of mental stress–induced myocardial ischemia to escitalopram treatment: Background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial

Abstract

Background Mental stress induced myocardial ischemia (MSIMI) is common in patients with clinically stable coronary heart disease (CHD) and is associated with poor outcomes. Depression is a risk factor of MSIMI. The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) trial investigates whether selective serotonin reuptake inhibitor (SSRI) treatment can improve MSIMI. The rationale and outline of the study are described. Method In this single center randomized clinical trial, adult patients with clinically stable CHD are recruited for baseline mental and exercise stress testing assessed by echocardiography. Additionally, psychometric questionnaires are administered and blood samples are collected for platelet activity analysis. Patients who demonstrate MSIMI, defined by new abnormal wall motion, ejection fraction reduction ≥8%, and/or development of ischemic ST change in electrocardiogram during mental stress testing, are randomized at a 1:1 ratio to escitalopram or placebo for 6 weeks. Approximately 120 patients with MSIMI are enrolled in the trial. The stress testing, platelet activity assessment and psychometric questionnaires are repeated at the end of the 6-week intervention. The hypothesis of the study is that SSRI treatment improves MSIMI via mood regulation and modification of platelet activity. Conclusion The REMIT study examines the effect of SSRI on MSIMI in vulnerable CHD patients and probes some potential underlying mechanisms.

Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia

“…14 Briefly, we screened all patients with CHD who visited Duke cardiology clinics. Adult patients aged ≥21 years with CHD, as documented by angiographic findings of coronary artery stenosis ≥70%, history of myocardial infarction, or history of cardiac revascularization were eligible for participation.…”

“…Exclusion criteria included significant cognitive impairment, life-threatening comorbidity (estimated 50% mortality within 1 year), active suicidal ideation, and psychiatric conditions precluding SSRI use. 14 Patients who exhibited MSIMI during baseline screening were qualified for the trial intervention.…”

“…14 Three mental stress tasks—mental arithmetic, mirror trace, and public speaking with anger recall—delivered in the same sequence throughout the study were used to assess MSIMI; each test was followed by a 6-minute rest.…”

“…19 Two clusters of emotional response to mental and exercise stress testing were obtained via a visual scale of 0–100: (1) positive emotions including calm and being in control, and (2) negative emotions including frustration, tension, and sadness. 14 …”

Psychological Stress and Induced Ischemic Syndromes

“…The REMIT placebo controlled randomized trial was designed to investigate whether treatment with escitalopram, a selective serotonin reuptake inhibitor (SSRI), can improve MSI 12 . The REMIT trial utilized myocardial performance (wall motion abnormality, left ventricular ejection fraction) assessed by echocardiography as the index of ischemia, and sequential administration of 3 mental stress tasks.…”