Abstract：
OBJECTIVE: Benefits of pharmacologic omega-3 fatty acid administration in cardiovascular prevention are controversial. Particularly, effects on coronary revascularization are unclear; also debated are specific benefits of eicosapentaenoic acid (EPA). We investigated incident coronary revascularizations, myocardial infarction (MI), stroke, heart failure (HF), unstable angina, and cardiovascular death, in subjects randomized to receive EPA or EPA + docosahexaenoic acid (EPA + DHA) vs. control.
RESULTS: Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (≥60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF.
CONCLUSIONS: Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research.
It is debated whether pharmacologic administration of omega-3 fatty acids reduces cardiac events. In particular, it is unclear whether benefits are actually restricted to the use of eicosapentaenoic acid (EPA), or whether combined administration of EPA + docosahexaenoic acid (DHA) is needed; furthermore, little is known about possible benefits of omega-3 fatty acids in reducing incidence of coronary revascularization procedures. In this meta-analysis of all published evidence of clinical trials comparing EPA alone or EPA + DHA vs. control (134 144 participants), we demonstrate the following: In the overall analysis of all trials, omega-3 supplementation reduced the risk of myocardial infarction and cardiovascular death, to a modest extent. However, when trials administering EPA alone were separately analysed, a further significant risk reduction for cardiovascular outcomes was demonstrated. Importantly, these benefits were also observed in subjects who were already taking statins as part of their chronic therapy.Administration of omega-3 fatty acids, particularly EPA alone, was also associated with a substantial decrease in the risk for subsequent coronary revascularizations. Reduction of revascularization procedures may induce additional benefits on overall health status and associated cost savings.
RESULTS: Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (≥60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF.
CONCLUSIONS: Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research.
It is debated whether pharmacologic administration of omega-3 fatty acids reduces cardiac events. In particular, it is unclear whether benefits are actually restricted to the use of eicosapentaenoic acid (EPA), or whether combined administration of EPA + docosahexaenoic acid (DHA) is needed; furthermore, little is known about possible benefits of omega-3 fatty acids in reducing incidence of coronary revascularization procedures. In this meta-analysis of all published evidence of clinical trials comparing EPA alone or EPA + DHA vs. control (134 144 participants), we demonstrate the following: In the overall analysis of all trials, omega-3 supplementation reduced the risk of myocardial infarction and cardiovascular death, to a modest extent. However, when trials administering EPA alone were separately analysed, a further significant risk reduction for cardiovascular outcomes was demonstrated. Importantly, these benefits were also observed in subjects who were already taking statins as part of their chronic therapy.Administration of omega-3 fatty acids, particularly EPA alone, was also associated with a substantial decrease in the risk for subsequent coronary revascularizations. Reduction of revascularization procedures may induce additional benefits on overall health status and associated cost savings.
摘要：
目的：在心血管疾病预防中使用ω-3脂肪酸的益处存在争议。特别是,对冠状动脉血运重建的影响尚不清楚;还有争议的是二十碳五烯酸(EPA)的具体益处.我们调查了偶然的冠状动脉血运重建，心肌梗死（MI），中风,心力衰竭(HF),不稳定型心绞痛,和心血管死亡，在随机接受EPA或EPA+二十二碳六烯酸（EPA+DHA）的受试者中，控制。
结果：在MEDLINE，Embase,Scopus,WebofScience,和科克伦图书馆搜索。遵循系统审查和荟萃分析指南的首选报告项目，以提取数据并评估数据质量和有效性。使用随机效应模型汇集数据。18项RCT，134144名参与者（初级和二级心血管预防）接受DHA+EPA（n=52498），仅EPA（n=14640），或对照/安慰剂（n=67006）包括在内。随访时间为4.5个月至7.4年。总的来说,与对照组相比，补充omega-3可降低血运重建的风险[0.90,95%置信区间(CI)0.84-0.98;P=0.001;P-异质性=0.0002;I2=68%],MI（0.89，95%CI0.81-0.98；P=0.02；P异质性=0.06；I2=41%），和心血管死亡（0.92，95％CI0.85-0.99；P=0.02；P异质性=0.13；I2=33％）。在大多数参与者（≥60％）接受他汀类药物治疗的试验中，仍观察到较低的风险。与DHA+EPA相比，仅EPA显示血运重建的风险进一步显着降低（0.76，95％CI0.65-0.88；P=0.0002；P-交互作用=0.005）和除HF以外的所有结果。
结论：补充Omega-3脂肪酸可降低心血管事件和冠状动脉血运重建的风险，无论使用他汀类药物的背景如何。单独的二十碳五烯酸产生更大的益处。特定omega-3分子在原发性与原发性中的作用二级预防以及减少血运重建对总体健康状况和成本节约的潜在益处值得进一步研究.
药物施用ω-3脂肪酸是否减少心脏事件存在争议。特别是,目前尚不清楚是否实际上仅限于使用二十碳五烯酸（EPA），或是否需要EPA+二十二碳六烯酸（DHA）的联合给药；此外，关于omega-3脂肪酸在降低冠状动脉血运重建手术发生率方面的可能益处知之甚少.在这项对所有已发表的临床试验证据的荟萃分析中，将EPA单独或EPADHA与控制（134144参与者），我们证明了以下几点：在所有试验的总体分析中，补充omega-3可降低心肌梗死和心血管死亡的风险，在适度的程度上。然而,当单独使用EPA的试验进行单独分析时，研究表明,心血管结局的风险进一步显著降低.重要的是,在已经将他汀类药物作为慢性治疗的一部分的受试者中也观察到了这些益处.服用omega-3脂肪酸，特别是EPA单独，还与随后的冠状动脉血运重建的风险大幅降低相关。减少血运重建程序可能会对总体健康状况和相关成本节省产生额外的益处。
结果：在MEDLINE，Embase,Scopus,WebofScience,和科克伦图书馆搜索。遵循系统审查和荟萃分析指南的首选报告项目，以提取数据并评估数据质量和有效性。使用随机效应模型汇集数据。18项RCT，134144名参与者（初级和二级心血管预防）接受DHA+EPA（n=52498），仅EPA（n=14640），或对照/安慰剂（n=67006）包括在内。随访时间为4.5个月至7.4年。总的来说,与对照组相比，补充omega-3可降低血运重建的风险[0.90,95%置信区间(CI)0.84-0.98;P=0.001;P-异质性=0.0002;I2=68%],MI（0.89，95%CI0.81-0.98；P=0.02；P异质性=0.06；I2=41%），和心血管死亡（0.92，95％CI0.85-0.99；P=0.02；P异质性=0.13；I2=33％）。在大多数参与者（≥60％）接受他汀类药物治疗的试验中，仍观察到较低的风险。与DHA+EPA相比，仅EPA显示血运重建的风险进一步显着降低（0.76，95％CI0.65-0.88；P=0.0002；P-交互作用=0.005）和除HF以外的所有结果。
结论：补充Omega-3脂肪酸可降低心血管事件和冠状动脉血运重建的风险，无论使用他汀类药物的背景如何。单独的二十碳五烯酸产生更大的益处。特定omega-3分子在原发性与原发性中的作用二级预防以及减少血运重建对总体健康状况和成本节约的潜在益处值得进一步研究.
药物施用ω-3脂肪酸是否减少心脏事件存在争议。特别是,目前尚不清楚是否实际上仅限于使用二十碳五烯酸（EPA），或是否需要EPA+二十二碳六烯酸（DHA）的联合给药；此外，关于omega-3脂肪酸在降低冠状动脉血运重建手术发生率方面的可能益处知之甚少.在这项对所有已发表的临床试验证据的荟萃分析中，将EPA单独或EPADHA与控制（134144参与者），我们证明了以下几点：在所有试验的总体分析中，补充omega-3可降低心肌梗死和心血管死亡的风险，在适度的程度上。然而,当单独使用EPA的试验进行单独分析时，研究表明,心血管结局的风险进一步显著降低.重要的是,在已经将他汀类药物作为慢性治疗的一部分的受试者中也观察到了这些益处.服用omega-3脂肪酸，特别是EPA单独，还与随后的冠状动脉血运重建的风险大幅降低相关。减少血运重建程序可能会对总体健康状况和相关成本节省产生额外的益处。
