长期补充海洋 ω-3 脂肪酸对心血管结局随机对照试验中心律失常风险的影响：系统评价和荟萃分析。
Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.
机构信息
Cardiology Division, Geneva University Hospitals, Switzerland (B.G.).
Institute of Primary Health Care (BIHAM), University of Bern, Switzerland (B.G.).
出版信息
Circulation. 2021 Dec 21;144(25):1981-1990. doi: 10.1161/CIRCULATIONAHA.121.055654. Epub 2021 Oct 6.
BACKGROUND
Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related.
METHODS
The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model.
RESULTS
Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; =0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; =0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; =0.024; for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of ɷ-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; =0.001).
CONCLUSIONS
In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.
背景
一些，但不是全部，大规模的随机对照试验（RCT）研究海洋 ω-3 脂肪酸补充剂对心血管结局的影响报告称心房颤动（AF）的风险增加。发现不同结果的潜在原因可能与剂量有关。
方法
检索了 2012 年 1 月 1 日至 2020 年 12 月 31 日期间 MEDLINE 和 Embase 数据库中的文章和摘要，此外还对 2019 年发表的大型心血管 RCT 的荟萃分析进行了检索。纳入了心血管结局的 RCT 海洋 ω-3 脂肪酸的 AF 结果报告，无论是作为预先指定的结局、不良事件还是住院原因，最小样本量为 500 例，中位随访时间至少 1 年。专门研究 ω-3 脂肪酸对已确诊 AF 或术后 AF 患者复发性 AF 的短期影响的 RCT 不包括在内。使用随机效应模型和 Knapp-Hartung 调整对每个试验中报告的 AF 结局的风险比（HR）进行荟萃分析，并使用荟萃回归模型评估剂量反应关系。
结果
在筛选的 4049 份记录中，有 7 项研究被纳入荟萃分析。其中，5 项已经在之前对心血管 RCT 的荟萃分析中发现。在来自 7 项试验的 81210 名患者中，58939 名（72.6%）接受了≤1g/d 的试验，22271 名（27.4%）接受了>1g/d 的 ω-3 脂肪酸试验。平均年龄为 65 岁，31842 名（39%）为女性。加权平均随访时间为 4.9 年。荟萃分析显示，使用海洋 ω-3 脂肪酸补充剂与 AF 风险增加相关（n=2905；HR，1.25[95%CI，1.07-1.46]；=0.013）。按剂量分层分析，>1g/d 试验的 HR 大于≤1g/d 试验（HR，1.49[95%CI，1.04-2.15]；=0.042）（交互检验<0.001）。在荟萃回归中，AF 的 HR 每增加 1g ω-3 脂肪酸剂量就会增加（HR，1.11[95%CI，1.06-1.15]；=0.001）。
结论
在检查心血管结局的 RCT 中，海洋 ω-3 补充剂与 AF 风险增加相关。在>1g/d 试验中，风险似乎更大。
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