Table 4.

Randomized Controlled Trials of Fish Intake and Omega-3 Ethyl Ester (EPA and DHA) 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
Diet and Reinfarction Trial20 1989 Post-MI Mean 41 days after MI	2,033 Male only	56.7 years 2 years	Welsh men	3 arms: fat intake 30% with ↑P/S fat ratio; cereal fiber 18g/d or 2-3 fish portions/week or 3,500 mg fish oil capsules daily	Total mortality CHD death	Those eating fish had 29% ↓ in total mortality (9.3% vs 12.8%, P<0.05 compared to other 2 groups Those in fish group had 32% ↓ in CHD death 7.7% vs 1.4%, P<0.01.
GISSI 21 1999 Post-MI within 3 months	5,664 15.3% female Women not reported separately; sex not adjusted for	3 months 3.5 years	Italian	850-882 mg EPA+DHA daily or none (open-label) TG: n-3: −4.6% vs 0.4% control; net: −4%	3 months 3.5 years	15%↓total death, nonfatal MI and nonfatal stroke RR: 0.85, 0.74-0.98, (P=0.02) due to 45% decrease in sudden death 0.55 (0.40–0.76) 20% ↓ in CVD death, nonfatal MI and stroke RR: 0.80, 95%CI: 0.68-0.95, P=0.008
GISSI HF22 2008 NYHA class II-IV heart failure	6,975 22% female Female not reported separately; sex not adjusted for	Mean (SD) age 67 (11) 3.9 yrs IQR: 3-4.5	Italian	850-882 mg EPA+DHA TG: net −6% in n-3 group	Total mortality	HR: 0·91; 95·5% CI: 0·833–0·998, P=0·041
Omega23 Post-MI 2010	3,851 25.6% female Did not report sex separately or adjust for sex	Mean age 64 1 year	104 German centers Race data not collected	460 mg EPA and 380 mg DHA vs 1 g olive oil placebo TG: n-3: −7% vs.- 3% placebo; net −4%	Sudden Cardiac death Total mortality Major adverse cerebrovascular and cardiovascular events Revascularization	1.5% vs 1.5%, P=0.84 4.6% vs 3.7%, P=0.18 10.4% and 8.8%, P=0.10 27.6% vs 29.1%, P=0.34
Alpha Omega24 2010 Post-MI on average 4 years	4,837 32% women Statin use 85%	mean age 69 years 40 months	32 hospitals in Holland	4 margarines: 226 mg of EPA+150 mg of DHA or ALA 1.9 g or EPA+DHA+ALA or Placebo TG: n-3: −5% vs. −3% for placebo; net: −2%	Major CVD events EPA+DHA Male EPA+DHA Women ALA Women	Major CVD events include fatal and nonfatal CVD, PCI and CABG HR:1.06; 95% CI: 0.89 to 1.25; P=0.51 HR: 0.82, 95% CI: 0.58-1.16, P=0.27 HR, 0.73; 95% CI: 0.51 to 1.03; P=0.07.
Origin25 2012 Primary and secondary prevention	12,536 all with DM or impaired fasting glucose 59% with CVD 34% female; didn’t report by sex or adjust for sex	63.5±7.8 years Median 6.2 years	40 countries; no race data	465 mg of EPA and 375 mg of DHA Placebo: 1 g olive oil TG: n-3: −17% vs. −6% for placebo; net: −11%	CVD death	n-3 vs placebo: 9.1% vs. 9.3%; HR: 0.98; 95% CI: 0.87-1.10; P=0.72
Risk and Prevention 26 2013 Primary and secondary prevention DM + at least 1 additional risk factor: 47.9% CVD: 29.5% 4 CVD risk factors but no DM: 20.8%	12,513 total 38.5% women 40% on statin	Mean age: 64 years Median follow-up: 5 years	860 general practitioners in Italy	Omega-3 ethyl ester 1 g daily or placebo (olive oil). Omega-3 ranged in a ratio of EPA:DHA 0.9:1 to 1.5:1). Baseline TG 150 mg/dL (range 107 to 201) TG decreased 28.2±1.3 mg/dL in omega-3 and 20.1±1.3 mg/dL in placebo, P<0.001.	Primary Endpoint Total group Men Women	Time to death from cardiovascular causes or hospital admission for cardiovascular causes Omega 3: 11.7% vs 11.9% placebo (aHR: 0.97; 95% CI: 0.88 to 1.08; P=0.58). 1.04 (0.92–1.17), P=NS 0.82 (0.67–0.99), P=0.04

Abbreviations: aHR indicates adjusted hazard ratio; ALA, alpha linolenic acid; CABG, coronary artery bypass graft; CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular disease; docosahexaenoic acid; DM, diabetes mellitus; EPA, eicosapentaenoic acid; g, gram; HF, heart failure; HR, hazard ratio; MI, myocardial infarction; n-3, omega-3; PCI, percutaneous coronary intervention; P/S, polyunsaturated/saturated; TG, triglyceride.