Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

By Deepak L. Bhatt, P. Steg, Michael Miller, E. Brinton, T. Jacobson, S. Ketchum, R. Doyle, R. Juliano, L. Jiao, C. Granowitz and 2 more. New England Journal of Medicine, 2019

2,542 citations recorded by the source corpus.

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double‐blind, placebo‐controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low‐density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end‐point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE‐IT ClinicalTrials.gov number, NCT01492361.)

Subfields: Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics, Surgery

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Citations in the corpus

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association (2023, background): “137 There have been conflicting results from trials of fish oil supplementation, and there are questions about the extent to which harm from the use of mineral oil in the control arm of the REDUCE-IT trial (Reduction of Cardiovascular Events With Icosapent Ethyl—Intervention Trial) contributed to…”
Fatty acids of microalgae: diversity and applications (2021, background): “Much attention is paid to the analysis of these problems (Swanson et al. 2012; Haimeur et al. 2016; Calder 2018; Bhatt et al. 2019; Harwood 2019; Sathasivam et al. 2019).”
Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society (2021, background): “ASCVD risk, although it was suggested that only a modest part of this benefit was due to changes in TRL levels.(176) The lack of benefit in”
Inflammation and atherosclerosis: signaling pathways and therapeutic intervention (2022, background): “Recent clinical trials suggested a reduction by approximately 25% in cardiovascular disease events, and an obvious return in low attenuation plaque volume.(324) Therefore, icosapent ethyl may be a good addition for patients with elevated TG levels to reduce LDL-C.”