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

Jun 26, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC, MBA; Kim A. Eagle, MD, MACC
Trial Sponsor:
Japan Heart Foundation
Date Presented:
11/06/2022
Date Published:
06/14/2024
Date Updated:
06/26/2024
Original Posted Date:
11/06/2022
References

Contribution To Literature:

Highlighted text has been updated as of June 26, 2024.

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

Description:

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

  • Randomized
  • Parallel
  • Open-label

Patients with chronic coronary artery disease on statin therapy were randomized to icosapent ethyl 1800 mg daily (n = 1,225) vs. control (n = 1,235).

  • Total number randomized: 2,460
  • 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)

Exclusion criteria:

  • Severe heart failure (left ventricular ejection fraction ≤30% or New York Heart Association class II-IV heart failure)
  • Active malignant disease
  • Active severe liver disease
  • Glycated hemoglobin >8.4%
  • Planned coronary intervention or surgery
  • Acute coronary syndrome and coronary revascularization within 3 months before enrollment
  • Active bleeding or bleeding diathesis

Principal Findings:

The primary outcome, cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina requiring emergency hospitalization, and coronary revascularization, occurred in 9.1% of the icosapent ethyl group vs. 12.6% of the control group (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.62-1.00; p = 0.055).

Secondary outcomes:

  • Sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization, and coronary revascularization: 6.6% in the icosapent ethyl group vs. 9.7% in the control group (HR 0.73, 95% CI 0.55-0.97)
  • Gastrointestinal disorders: 3.4% in the icosapent ethyl group vs. 1.2% in the control group (p < 0.001)
  • New-onset atrial fibrillation: 3.1% in the icosapent ethyl group vs. 1.6% in the control group (p = 0.017)

Interpretation:

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 and new-onset atrial fibrillation were more frequent in the icosapent ethyl group compared with control. 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.

References:

Miyauchi K, Iwata H, Nishizaki Y, et al., on behalf of the RESPECT-EPA Investigators. Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid (RESPECT-EPA). Circulation 2024;Jun 14:[Epub ahead of print].

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

Clinical Topics: Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Prevention

Keywords: AHA Annual Scientific Sessions, AHA22, Coronary Artery Disease, Eicosapentaenoic Acid, Hydroxymethylglutaryl-CoA Reductase Inhibitors


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