Table 5.

Randomized Controlled Trials of Pure EPA Supplementation in Primary and/or Secondary Prevention of CVD by Sex and Race

Study Year	# subjects Female/male	Mean age Follow-up	Race ethnicity	Characteristics (exposure) n-3 type and dosage Baseline TG and % reduction	Endpoint	Outcome of the exposure or intervention
JELIS 27 2007 Primary and secondary prevention	18,645 total 12,786 women (69%) 5,859 men	61±8 years 4.6 years	Japanese	1800 mg icosapent ethyl+ statin or statin only; open-label On Prava 10 or 20 mg or simva 5 or 10 mg Baseline TG: 153.2 mg/dL TG: n-3: −9% vs. −4% (control); net: −5% Mean LDL-C: 180 mg/dL	Major coronary events Primary prevention group Total group CAD group Women Men	Coronary events include sudden cardiac death, fatal and nonfatal MI, unstable angina, PCI and CABG 18% ↓; HR:0.82; 95% CI: 0·63–1.06, P=0.132 19% ↓; HR: 0·81; 95% CI: 0·69–0·95; P=0.011 19% ↓; HR:0.81; 95% CI: 0.657–0.998, P=0.048 13% ↓; HR: 0.87; 95% CI: 0.68–1.13 24% ↓; HR: 0.76; 95% CI: 0.62–0.94
RESPECT-EPA 28,29 DM: 45% All with CAD	2,506 17.3% women n-3: 1,249 control: 1,257 EPA/AA ratio < 0.4 All on statin	Median [IQR] age: 68 (61.0, 73.0) Follow-up: 6 years	95 centers in Japan	Purified EPA; 1800 mg daily vs none (open label) Baseline median TG: EPA: 120 mg/dL; control: 117 mg/dL TG reduction not given Median LDL-C: 80 mg/dL Median EPA: 45 μg/ml	Primary endpoint Secondary endpoint	Cardiovascular death, non-fatal MI, non-fatal ischemic stroke, unstable angina pectoris requiring hospitalization, and clinically indicated coronary revascularization 10.9% versus 14.9%, HR 0.785, P=0.0547). Sudden cardiac death, MI, unstable angina, and coronary revascularization 8.0% versus 11.3%, HR 0.734, P=0.0306)
REDUCE-IT 201930 202131 CAD 70.7% T2DM 29.3% with at least 1 additional risk factor All with TG 135–499 mg/dL;	5,822 men 2,357 women	Median [IQR] 64 [57-69] Median follow-up 4.9 years	90.3% white median TG of 216.5 mg/dL TG reduction: EPA: −18.3% vs. +2.2% in placebo; net −20.5% for EPA	4 g icosapent ethyl vs mineral oil placebo Primary Prevention Secondary Prevention Central adjudication30 Investigator adjudication31 Central adjudication30 Investigator adjudication31 Central adjudication30 Central adjudication30	Primary endpoint Total group30 Men Women White race Other race	CVD death, nonfatal MI, nonfatal stroke, PCI or CABG, unstable angina HR: 0.88; 95% CI: 0.70–1.10 HR: 0.73; 95%CI: 0.65–0.81 HR: 0.73; 95% CI: 0.65-0.82 HR: 0.74; 95% CI: 0.67-0.82 HR: 0.82; 95% CI: 0.66-0.1.01 HR: 0.74; 95% CI: 0.61-0.89 HR: 0.77; 95% CI: 0.69–0.85 HR: 0.60; 95% CI: 0.43–0.83

Abbreviations: CABG indicates coronary artery bypass graft; CAD, coronary artery disease; CI, confidence interval; CVD, cardiovascular disease; DM, diabetes mellitus; EPA, eicosapentaenoic acid; g, gram; HR, hazard ratio; MI, myocardial infarction; n-3, omega-3; PCI, percutaneous coronary intervention; REDUCE-IT, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial; TG, triglyceride.