Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Australia.
Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
JAMA. 2020 Dec 8;324(22):2268-2280. doi: 10.1001/jama.2020.22258.
It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk.
To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa.
Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins.
The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.
When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%).
Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients.
ClinicalTrials.gov Identifier: NCT02104817.
欧米伽 3 脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）是否能降低心血管风险仍不确定。
确定羧酸形式的 EPA 和 DHA（ω-3 CA）对动脉粥样硬化性血脂异常和高心血管风险患者的脂质和炎症标志物具有有利影响，从而对心血管结局的影响。
设计、设置和参与者： 一项双盲、随机、多中心试验（招募时间为 2014 年 10 月 30 日至 2017 年 6 月 14 日；研究终止时间为 2020 年 1 月 8 日；最后一次患者就诊时间为 2020 年 5 月 14 日），比较高心血管风险、高甘油三酯血症和低高密度脂蛋白胆固醇（HDL-C）水平的他汀类药物治疗患者中 ω-3 CA 与玉米油的效果。共有 13078 名患者在北美、欧洲、南美、亚洲、澳大利亚、新西兰和南非的 675 家学术和社区医院被随机分组。
参与者被随机分配每天服用 4 g 的 ω-3 CA（n = 6539）或玉米油（n = 6539），后者旨在作为惰性对照剂，同时还接受包括他汀类药物在内的常规背景治疗。
主要疗效指标是心血管死亡、非致死性心肌梗死、非致死性卒中、冠状动脉血运重建或需要住院治疗的不稳定型心绞痛的复合结果。
当 1384 名患者出现主要终点事件（计划 1600 名事件中的 1 名）时，根据中期分析表明 ω-3 CA 与玉米油对照剂相比不太可能有临床获益，该试验提前停止。在 13078 名接受治疗的患者（平均[标准差]年龄，62.5[9.0]岁；35%女性；70%患有糖尿病；中位低密度脂蛋白[LDL]胆固醇水平，75.0 mg/dL；中位甘油三酯水平，240 mg/dL；中位 HDL-C 水平，36 mg/dL；中位高敏 C 反应蛋白水平，2.1 mg/L）中，12633 名（96.6%）完成了试验并确定了主要终点状态。ω-3 CA 组有 785 名患者（12.0%）发生主要终点事件，而玉米油组有 795 名患者（12.2%）发生主要终点事件（风险比，0.99 [95%CI，0.90-1.09]；P =.84）。ω-3 CA 组（24.7%）比玉米油治疗组（14.7%）更常见胃肠道不良事件。
在高心血管风险的他汀类药物治疗患者中，与玉米油相比，ω-3 CA 联合常规背景治疗，在主要不良心血管事件的复合结局方面无显著差异。这些发现不支持使用这种欧米伽 3 脂肪酸配方来降低高危患者的主要不良心血管事件。
ClinicalTrials.gov 标识符：NCT02104817。
