TY - JOUR

T1 - Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia

AU - Bhatt, Deepak L.

AU - Steg, P. Gabriel

AU - Miller, Michael

AU - Brinton, Eliot A.

AU - Jacobson, Terry A.

AU - Ketchum, Steven B.

AU - Doyle, Ralph T.

AU - Juliano, Rebecca A.

AU - Jiao, Lixia

AU - Granowitz, Craig

AU - Tardif, Jean Claude

AU - Ballantyne, Christie M.

AU - REDUCE-IT Investigators

AU - Перепеч, Никита Борисович

PY - 2019/1/3

Y1 - 2019/1/3

N2 - 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.

AB - 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.

KW - Aged

KW - Cardiovascular Diseases/mortality

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Eicosapentaenoic Acid/analogs & derivatives

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Hypertriglyceridemia/drug therapy

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Platelet Aggregation Inhibitors/therapeutic use

KW - Risk Factors

KW - Secondary Prevention

KW - Triglycerides/blood

KW - METAANALYSIS

KW - CHOLESTEROL

KW - TRIGLYCERIDES

KW - ESTER AMR101 THERAPY

KW - ATHEROSCLEROSIS

KW - INFARCTION

KW - STATIN THERAPY

KW - CORONARY-HEART-DISEASE

KW - EICOSAPENTAENOIC ACID

KW - PRIMARY PREVENTION

UR - http://www.scopus.com/inward/record.url?scp=85058215650&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/trial-protocol-provided-authors-give-readers-additional-information-about-work-protocol-bhatt-dl-ste

U2 - 10.1056/NEJMoa1812792

DO - 10.1056/NEJMoa1812792

M3 - Article

C2 - 30415628

AN - SCOPUS:85058215650

VL - 380

SP - 11

EP - 22

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 1

ER -