Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

被引:2263
作者
Bhatt, Deepak L. [1 ,2 ]
Steg, P. Gabriel [3 ,4 ]
Miller, Michael [5 ]
Brinton, Eliot A. [6 ]
Jacobson, Terry A. [7 ]
Ketchum, Steven B. [8 ]
Doyle, Ralph T., Jr. [8 ]
Juliano, Rebecca A. [8 ]
Jiao, Lixia [8 ]
Granowitz, Craig [8 ]
Tardif, Jean-Claude [9 ]
Ballantyne, Christie M. [10 ,11 ]
机构
[1] Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA
[2] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA
[3] Univ Paris Diderot, Hop Bichat, AP HP,INSERM,U1148, FACT,Dept Hosp Univ FIRE Fibrose Inflammat & Remo, Paris, France
[4] Imperial Coll, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England
[5] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[6] Utah Lipid Ctr, Salt Lake City, UT USA
[7] Emory Univ, Sch Med, Dept Med, Off Hlth Promot & Dis Prevent, Atlanta, GA USA
[8] Amarin Pharma, Bedminster, NJ USA
[9] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada
[10] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[11] Methodist De Bakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA
关键词
CORONARY-HEART-DISEASE; ESTER AMR101 THERAPY; EICOSAPENTAENOIC ACID; PRIMARY PREVENTION; STATIN THERAPY; CHOLESTEROL; ATHEROSCLEROSIS; TRIGLYCERIDES; METAANALYSIS; INFARCTION;
D O I
10.1056/NEJMoa1812792
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:11 / 22
页数:12
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