Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
Cardiovasc Drugs Ther. 2024 Aug;38(4):799-817. doi: 10.1007/s10557-022-07379-z. Epub 2022 Sep 14.
It is widely accepted that omega-3 fatty acids are beneficial in the prevention of cardiovascular disease, but many large randomized controlled trial studies and meta-analyses have come to different conclusions. The evidence for omega-3 fatty acids supplementation to prevent cardiovascular disease remains insufficient. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of several types of omega-3 fatty acids supplements.
We comprehensively searched the online database and found 15 RCTs. The primary efficacy outcomes included major cardiovascular events, myocardial infarction, heart failure, atrial fibrillation, stroke, cardiovascular death, and all-cause death. The safety endpoints included gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis was conducted according to the main characteristics of the population, and the dose-response relationship of omega-3 fatty acids was evaluated by meta-regression. All results were calculated by the random effect model. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics.
The incidence of major cardiovascular events (RR 0.95, 95%CI 0.91 to 0.99, P = 0.026), myocardial infarction (RR 0.90, 95%CI 0.83 to 0.98; P = 0.021), and cardiovascular death (RR 0.94, 95%CI 0.88 to 0.99; P = 0.028) was reduced in the omega-3 fatty acid group compared with the control group. An increased risk of atrial fibrillation (RR 1.25, 95%CI 1.10 to 1.41; P = 0.000) was observed in patients in the omega-3 fatty acid group. No statistical differences were observed between the two groups in heart failure, stroke, and all-cause death. For safety endpoints, there were no statistically significant differences between the two groups in gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis showed that the cardiovascular benefit of omega-3 fatty acids was primarily attributable to the prescription of EPA ethyl ester. Omega-3 fatty acids may reduce the risk of major cardiovascular events in patients with cardiovascular disease or risk factors, and reduce the risk of myocardial infarction in patients without cardiovascular disease; however, they may increase the risk of stroke in patients with myocardial infarction. In addition, prescription omega-3 acid ethyl ester has a good safety profile, and prescription EPA ethyl ester has a high risk of bleeding.
Moderate evidence showed that the use of omega-3 fatty acids may reduce the risk of major cardiovascular events, myocardial infarction, and cardiovascular death. Compared to other types of omega-3 fatty acids supplements, we support the use of prescription EPA ethyl ester formulations for the prevention of cardiovascular disease, but the potential risk of atrial fibrillation and bleeding cannot be ignored. It is important to note that omega-3 fatty acids should be applied with caution in patients with previous myocardial infarction, which may increase the risk of stroke. Finally, omega-3 fatty acids are relatively safe and in general do not increase gastrointestinal problems, bleeding-related disorders, or cancer, but attention needs to be paid to the risk of bleeding with prescription EPA ethyl ester formulations.
人们普遍认为ω-3 脂肪酸有益于预防心血管疾病，但许多大型随机对照试验研究和荟萃分析得出了不同的结论。ω-3 脂肪酸补充剂预防心血管疾病的证据仍然不足。我们进行了系统评价和荟萃分析，以评估几种类型的 ω-3 脂肪酸补充剂的疗效和安全性。
我们全面搜索了在线数据库，发现了 15 项 RCT。主要疗效终点包括主要心血管事件、心肌梗死、心力衰竭、心房颤动、中风、心血管死亡和全因死亡。安全性终点包括胃肠道问题、出血相关疾病和癌症。根据人群的主要特征进行亚组分析，并通过荟萃回归评估 ω-3 脂肪酸的剂量-反应关系。所有结果均采用随机效应模型计算。使用卡方检验评估统计异质性，并使用 I 平方统计量化。
与对照组相比，ω-3 脂肪酸组的主要心血管事件（RR 0.95，95%CI 0.91 至 0.99，P = 0.026）、心肌梗死（RR 0.90，95%CI 0.83 至 0.98；P = 0.021）和心血管死亡（RR 0.94，95%CI 0.88 至 0.99；P = 0.028）的发生率降低。ω-3 脂肪酸组心房颤动（RR 1.25，95%CI 1.10 至 1.41；P = 0.000）的风险增加。两组间心力衰竭、中风和全因死亡无统计学差异。对于安全性终点，两组间胃肠道问题、出血相关疾病和癌症无统计学差异。亚组分析显示，ω-3 脂肪酸的心血管益处主要归因于 EPA 乙酯的处方。ω-3 脂肪酸可能降低心血管疾病或危险因素患者的主要心血管事件风险，并降低无心血管疾病患者的心肌梗死风险；然而，它们可能会增加心肌梗死患者中风的风险。此外，处方ω-3 酸乙酯具有良好的安全性，处方 EPA 乙酯有较高的出血风险。
中等证据表明，使用 ω-3 脂肪酸可能降低主要心血管事件、心肌梗死和心血管死亡的风险。与其他类型的 ω-3 脂肪酸补充剂相比，我们支持使用处方 EPA 乙酯制剂预防心血管疾病，但不能忽视心房颤动和出血的潜在风险。需要注意的是，ω-3 脂肪酸在既往心肌梗死患者中应用应谨慎，可能会增加中风风险。最后，ω-3 脂肪酸相对安全，一般不会增加胃肠道问题、出血相关疾病或癌症，但需要注意处方 EPA 乙酯制剂的出血风险。
