Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid - RESPECT-EPA

Contribution To Literature:

The RESPECT-EPA trial showed that icosapent ethyl may reduce adverse cardiovascular outcomes when added to statin therapy.


The goal of the trial was to evaluate icosapent ethyl, a purified eicosapentaenoic acid (EPA), compared with control among patients with chronic coronary artery disease treated with statin therapy.

Study Design

  • Randomization
  • Parallel
  • Open-label

Patients with chronic coronary artery disease on statin therapy were randomized to icosapent ethyl 1800 mg daily (n = 1,249) vs. control (n = 1,257).

  • Total number of enrollees: 2,506
  • Duration of follow-up: 5 years
  • Mean patient age: 68 years
  • Percentage female: 17%
  • Percentage with diabetes: 45%

Inclusion criteria:

  • 20-79 years of age
  • Chronic coronary artery disease
  • Statin therapy for at least 1 month
  • Low EPA/AA (arachidonic acid) ratio (<0.4)

Principal Findings:

The primary outcome, cardiovascular death, myocardial infarction, stroke, unstable angina requiring hospitalization, and revascularization, occurred in 10.9% of the icosapent ethyl group vs. 14.9% of the control group (p = 0.055).

Secondary outcomes:

  • Sudden cardiac death, myocardial infarction, unstable angina, or coronary revascularization: 8.0% in the icosapent ethyl group vs. 11.3% in the control group (p = 0.031)
  • Gastrointestinal disorders: 3.4% in the icosapent ethyl group vs. 1.2% in the control group (p < 0.001)


Among Japanese patients with chronic coronary artery disease treated with statin therapy, icosapent ethyl may be associated with a reduction in adverse cardiovascular outcomes. Gastrointestinal disorders were more frequent in the icosapent ethyl group compared with control, as was atrial fibrillation. Important limitations of this trial include that it was underpowered and not placebo controlled. Nevertheless, the results are consistent with JELIS and REDUCE-IT trials in showing a beneficial effect on cardiovascular endpoints with icosapent ethyl.


Presented by Dr. Hiroyuki Daida at the American Heart Association Scientific Sessions, Chicago, IL, November 6, 2022.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease

Keywords: AHA Annual Scientific Sessions, AHA22, Angina, Unstable, Arachidonic Acid, Atrial Fibrillation, Coronary Artery Disease, Death, Sudden, Cardiac, Eicosapentaenoic Acid, Gastrointestinal Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Primary Prevention, Secondary Prevention, Stroke

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