The effect of omega-3 Polyunsaturated Fatty Acid (PUFA) prescription preparations on the prevention of clinical cardiovascular disease: a meta-analysis of RCTs

Evidence from systematic reviews of the cardioprotective effect of omega-3 polyunsaturated fatty acid (PUFA) remains controversial, and interventions including PUFAs dietary supplements or prescription medications cannot accurately reflect the role of PUFA RX in cardiovascular disease (CVD) prevention. We conducted a meta-analysis of randomized clinical trials (RCTs) to evaluate the efficacy of PUFA prescription medication in preventing CVD. Two reviewers conducted a literature search of Embase, MEDLINE/PubMed, and the Cochrane Library from their inception to September 2023. The inclusion criteria were RCTs evaluating long-term supplementation (≥ 1 year) with PUFA prescriptions and reporting cardiovascular outcomes. Data were extracted independently by two authors, and the certainty of evidence for each outcome was assessed using the GRADE system. Random-effects models were used to estimate the risk ratios (RRs) and 95% confidence intervals (CIs). The primary outcomes were cardiovascular events. Secondary endpoints included major adverse cardiovascular events (MACEs), cardiac death, all-cause mortality, myocardial infarction, stroke, and revascularization. Subgroup analyses were performed based on PUFA components, dosage, follow-up duration, and risk status. Twelve RCTs involving 99,830 participants were included. The mean age of participants ranged from 59.4 to 74.0 years, with a follow-up period varying from 1 to 6.2 years. Compared with placebo and statins, PUFA prescription medication was associated with a reduced risk of cardiovascular events (8 RCTs, n = 75,929, RR, 0.88 [95% CI, 0.81–0.95]; P = 0.0007; I 2 = 45%), cardiac death (10 RCTs, n = 95,440, RR, 0.91 [95% CI, 0.84–0.99]; P = 0.02; I 2 = 23%), myocardial infarction (9 RCTs, n = 94,877, RR, 0.84 [95% CI, 0.73–0.96]; P = 0.009; I 2 = 62%), and revascularization (9 RCTs, n = 91,242, RR, 0.91 [95% CI, 0.84–0.99]; P = 0.02; I 2 = 63%). PUFA prescription medication could lower the risks of cardiovascular events, cardiac death, myocardial infarction and revascularization. This research provides insight into the efficacy of PUFA prescription medications in CVD prevention and contributes to the ongoing debate on the role of PUFA products in cardiovascular outcomes.