REDUCE-IT USA Results From the 3146 Patients Randomized in the United States

• Authors: Deepak L. Bhatt, Harvard Medical School; Michael Miller, University of Maryland; Eliot A. Brinton, Utah Lipid Center; Terry Jacobson, Emory University; Ph. Gabriel Steg, Université de Paris; Steven B. Ketchum, Amarin Pharma Inc; Ralph T. Doyle, Amarin Pharma Inc; Rebecca A. Juliano, Amarin Pharma Inc; Lixia Jiao, Amarin Pharma Inc; Craig Granowitz, Amarin Pharma Inc; Jean-Claude Tardif, University of Montreal; Brian Olshansky, University of Iowa; Mina K. Chung, Cleveland Clinic; C. Michael Gibson, Beth Israel Deaconess Medical Center; Robert P. Giugliano, Harvard Medical School; Matthew J. Budoff, Harbor UCLA Medical Center; Christie M. Ballantyne, Baylor College of Medicine
• Journal Title: Circulation
• Volume: Volume 141, Number 5
• Publisher: Wolters Kluwer Health, Inc. | 2020-02-04, Pages 367-375
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1161/CIRCULATIONAHA.119.044440
• Subjects: Health Sciences, Health Care Management; Health Sciences, Rehabilitation and Therapy; Health Sciences, Occupational Health and Safety
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Peripheral Vascular Disease; Cardiovascular System & Cardiology; eicosapentaenoic acid ethyl ester; fatty acids, omega-3; lipids; prevention and control; triglycerides; United States; Icosapent ethyl; Clinical trial; Heart failure; Cardiovascular risk; Events; Outcomes; Triglycerides; Clopidogrel; Prevalence; Ticagrelor

Abstract

Background: Some trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States. Methods: REDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points. Results: A total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort. Conclusions: Whereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.