Maki Kevin C, Guyton John R, Orringer Carl E, Hamilton-Craig Ian, Alexander Dominik D, Davidson Michael H
Midwest Center for Metabolic and Cardiovascular Research/MB Clinical Research, Glen Ellyn, IL, USA.
Duke University School of Medicine, Durham, NC, USA.
J Clin Lipidol. 2016 Jul-Aug;10(4):905-914. doi: 10.1016/j.jacl.2016.03.008. Epub 2016 Mar 23.
Cardiovascular outcomes trials of fibrates, niacin, or omega-3 fatty acids alone, or added to a statin, have not consistently demonstrated reduced risk, but larger, statistically significant clinical benefits have been reported in subgroups with elevated triglycerides (TG) and/or elevated TG plus low high-density lipoprotein cholesterol (HDL-C).
To perform a meta-analysis of the effects of therapies targeting TG and TG-rich lipoprotein cholesterol on cardiovascular disease event risk in subjects with elevated TG or elevated TG paired with low HDL-C.
Publications were identified using PubMed, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Internet Stroke Center. Random-effects meta-analysis models were used to generate summary relative risk estimates and 95% confidence intervals. Heterogeneity was assessed by χ(2) and I(2) statistics, and the impact of each trial was assessed in one study-removed sensitivity analyses.
Six trials of fibrates, 2 of niacin, 1 of fibrate + niacin, and 1 of omega-3 eicosapentaenoic acid ethyl esters were identified. For the prespecified primary cardiovascular disease or coronary heart disease end point used in each trial, the summary relative risk estimate (95% confidence interval) for subjects with elevated TG was 0.82 (0.73-0.91), p-heterogeneity = 0.13, I(2) = 36.2, and for subjects with elevated TG and low-HDL-C, it was 0.71 (0.63-0.81), p-heterogeneity = 0.52, I(2) = 0.0. There was no evidence of publication bias, and the results remained statistically significant when each individual trial was removed.
Drugs that substantially, but not exclusively, lower TG and TG-rich lipoprotein cholesterol may have cardiovascular benefits in individuals with elevated TG, particularly if accompanied by low HDL-C.
贝特类药物、烟酸或ω-3脂肪酸单独使用或与他汀类药物联合使用的心血管结局试验,并未始终证明能降低风险,但在甘油三酯(TG)升高和/或TG升高合并高密度脂蛋白胆固醇(HDL-C)降低的亚组中,已报告有更大的、具有统计学意义的临床益处。
对针对TG和富含TG的脂蛋白胆固醇的疗法对TG升高或TG升高合并HDL-C降低的受试者心血管疾病事件风险的影响进行荟萃分析。
通过PubMed、Cochrane对照试验中央注册库、clinicaltrials.gov、世界卫生组织国际临床试验注册平台和互联网卒中中心识别出版物。采用随机效应荟萃分析模型生成汇总相对风险估计值和95%置信区间。通过χ²和I²统计量评估异质性,并在一项逐一剔除研究的敏感性分析中评估每项试验的影响。
识别出6项贝特类药物试验、2项烟酸试验、1项贝特类药物+烟酸试验和1项ω-3二十碳五烯酸乙酯试验。对于每项试验中预先设定的主要心血管疾病或冠心病终点,TG升高的受试者的汇总相对风险估计值(95%置信区间)为0.82(0.73 - 0.91),p异质性 = 0.13,I² = 36.2,而TG升高且HDL-C降低的受试者为0.71(0.63 - 0.81),p异质性 = 0.52,I² = 0.0。没有发表偏倚的证据,并且在逐一剔除每项个体试验时结果仍具有统计学意义。
能大幅但非唯一降低TG和富含TG的脂蛋白胆固醇的药物,可能对TG升高尤其是伴有HDL-C降低的个体具有心血管益处。