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Cited by 57Fatty Acid Research and HealthLipoproteins and Cardiovascular HealthAntiplatelet Therapy and Cardiovascular Diseases

Reduction in Revascularization With Icosapent Ethyl: Insights From REDUCE-IT Revascularization Analyses

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Peterson, Benjamin E., Bhatt, Deepak L., Steg, Ph. Gabriel, Miller, Michael, Brinton, Eliot A., Jacobson, Terry A., Ketchum, Steven B., Juliano, Rebecca A. +11 more·2021·Circulation
DOI 10.1161/circulationaha.120.050276PMC PMC7752247
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Abstract

Background: Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations. Methods: REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135–499 mg/dL), controlled low-density lipoprotein (41–100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes. Results: A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58–0.76]; P <0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56–0.74]; P <0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59–0.79]; P <0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45–0.81]; P =0.0005). Conclusions: Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non–low-density lipoprotein–lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

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  • Patients treated with icosapent ethyl had a 26% relative risk reduction in the composite of cardiovascular death, myocardial infarction, or stroke.

    “The study further demonstrated that patients treated with icosapent ethyl had a 26% relative risk reduction in the composite of cardiovascular death, myocardial infarction, or stroke.”

    From Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL (2021) · cites this paper as [18]

    The Introduction reports a 26% relative risk reduction in REDUCE-IT’s key secondary endpoint with icosapent ethyl versus placebo. However, our copy does not define that endpoint as the composite of cardiovascular death, myocardial infarction, and stroke; the Methods define only the five-component primary endpoint. The claimed percentage is supported, but the specified composite is not established by this paper’s text. (LLM, conf=0.83)

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  • The gains in life expectancy from cardiovascular causes correlate with improvement in nonfatal MI, CHD events, MACE, and revascularization.

    “The gains in life expectancy from cardiovascular causes correlate with improvement in nonfatal MI, CHD events, MACE, and revascularization [22].”

    From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [22]

    The Introduction reports reductions in the trial’s primary cardiovascular endpoint, and the Results report fewer coronary revascularizations with icosapent ethyl; the Discussion also reports fewer myocardial infarctions. But the paper does not report gains in life expectancy or test whether such gains correlate with improvements in these outcomes (searched for life expectancy and the proposed correlation). (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • After a median follow-up of 4.9 years, the study drug demonstrated a 25% relative risk reduction in the primary composite end point of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina.

    “After a median follow-up period of 4.9 years, the study drug demonstrated a 25% relative risk reduction in the primary composite end point of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina.”

    From Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL (2021) · cites this paper as [18]

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References 56 · Cited by 57

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Authors
Peterson, B. E., Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Juliano, R. A., Jiao, L., Doyle, R. T., Granowitz, C., Gibson, C. M., Pinto, D., Giugliano, R. P., Budoff, M. J., Tardif, J.-C., Verma, S., Ballantyne, C. M., & On behalf of the REDUCE-IT Investigators
Affiliations
  • Brigham and Women's Hospital (US)
  • Université de Paris, AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), INSERM U-1148, France (Ph.G.S.).
  • University of Maryland, Baltimore (US)
  • Utah Lipid Center, Salt Lake City (E.A.B.).
  • Emory University (US)
  • Amarin (United States) (US)
  • Baim Institute for Clinical Research (US)
  • The Lundquist Institute (US)
  • Montreal Heart Institute (CA)
  • St. Michael's Hospital (CA)
  • Baylor College of Medicine (US)
Corresponding author
Bhatt, Deepak L.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-01-05
Volume
143
Issue
1
Pages
33-44
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.120.050276
PMC
PMC7752247
OpenAlex
W3115888582
Cited by
57
References
56
Citations by year
2026: 2 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 21 · 2021: 16 · 2020: 1
FWCI
6.95
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Circulation (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
National Heart, Lung, and Blood Institute (T32HL007604)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Keywords
icosapent ethyl, triglyceride elevation, coronary revascularization, percutaneous coronary intervention, coronary artery bypass grafting, statin-treated patients, cardiovascular risk, REDUCE-IT trial, triglyceride-lowering therapy, urgent revascularization, diabetes mellitus
MeSH terms
Aged, Cardiovascular Diseases, Diabetes Mellitus, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Revascularization, Platelet Aggregation Inhibitors, Eicosapentaenoic Acid, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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