JAMA:ω-3脂肪酸预防心脏手术后房颤

　　背景  术后房颤或房扑（AF）是心脏手术的最常见并发症之一，可导致并发症发生率和医疗保健资源利用显著增加。一些小型试验针对长链n-3-多不饱和脂肪酸（PUFA）是否能够减少术后AF进行了评价，但结果不一。

　　目的  本研究旨在确定围手术期补充n-3-PUFA能否减少术后AF。

　　设计、条件和患者  ω-3脂肪酸预防术后房颤（OPERA）双盲、安慰剂对照、随机临床试验。研究于2010年8月至2012年6月在美国、意大利和阿根廷28个研究中心共纳入1516例拟行心脏手术的患者。纳入标准宽泛，主要排除标准为入组时规律服用鱼油或缺乏窦性心律的患者。

　　干预  患者随机接受鱼油（含≥840 mg乙酯化n-3-PUFA的1 g胶囊）或安慰剂，术前经过3~5天达到10 g负荷剂量（或经过2天达到8 g），术后给予2 g/d直至出院或术后10天（以先发生者为准）。

　　主要转归指标  术后发生持续时间超过30 秒的AF。次要终点为持续时间超过1小时、有症状表现或需进行心脏复律治疗的术后AF；不包括房扑的术后AF；首次术后AF发生时间；每例患者的AF发作次数；住院治疗；以及主要心血管不良事件、30天死亡率、出血和其他不良事件。

　　结果  入组时，患者平均年龄为64岁（SD，13）；男性占72.2%，51.8%的患者计划行瓣膜手术。研究中，233例（30.7%）安慰剂组患者和227例（30.0%）n-3-PUFA组患者出现主要终点[比值比，0.96（95% CI，0.77~1.20）；P =0.74]。安慰剂组和鱼油组的次要终点发生率均无显著差异，包括持续性、有症状或需治疗的术后AF [231（30.5%）对224（29.6%），P =0.70]或每例患者的术后AF发作次数[1次发作：156（20.6%）对157（20.7%）；2次发作：59（7.8%）对49（6.5%）；≥3次发作：18（2.4%）对21（2.8%）]（P =0.73）。补充n-3-PUFA治疗普遍耐受性良好，没有出血或严重不良事件危险增加的证据。

　　结论  这项针对进行心脏手术的患者的大型多国试验显示，与安慰剂相比，围手术期补充n-3-PUFA并不会降低术后AF的危险。

Fish Oil and Postoperative Atrial Fibrillation

The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial

Context  

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.

Objective  

To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.

Design, Setting, and Patients  

The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment.

Intervention  

Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.

Main Outcome Measure  

Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events.

Results  

At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Conclusion  

In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF.

Trial Registration  

clinicaltrials.gov Identifier: NCT00970489