Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

Meta-analysis of randomized controlled trials in high-risk cardiovascular patients, including post-myocardial infarction patients, patients with implantable cardioverter-defibrillators, diabetics, and other high-risk cardiovascular groups. Mortality analyses included 34,501 randomized participants (17,276 omega-3; 17,190 controls) from 15 studies, and restenosis analyses after PCI included 3,553 randomized participants (1,817 omega-3; 1,736 controls) from 14 studies.

Omega-3 fatty acid supplementation was evaluated across trials using EPA, DHA, DPA, or ALA. Doses ranged from 0.9 g/day to 6.9 g/day in mortality studies and from 3 g/day to 6.9 g/day in post-PCI restenosis studies; route was oral and follow-up ranged from 1 to 55 months.

Omega-3 supplementation did not produce statistically significant reductions in all-cause mortality or restenosis after PCI, although the point estimates suggested a possible modest benefit. All-cause mortality was RR = 0.88, 95% CrI = 0.64, 1.03, with a probability of some benefit of 0.93. Restenosis after PCI was RR = 0.89, 95% CrI = 0.72, 1.05, with a probability of some benefit of 0.90. Safety was generally favorable, but gastrointestinal side effects were more common with omega-3 (RR = 1.29, 95% CrI = 1.02, 1.61), while treatment discontinuation, malignancy, and bleeding were not clearly increased.

Trials were heterogeneous in patient population, omega-3 form, dose, and follow-up duration, which ranged from 1 to 55 months. Apparent benefits were attenuated in larger and longer trials, suggesting possible bias or small-study effects. Adverse-event reporting was incomplete, and some outcomes were informed by relatively few studies.