A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes
A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes
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DOI：
10.1177/2047487318766612
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发表时间：
2018-05-01
影响因子：
8.3
通讯作者：
Krasuski, Richard
中科院分区：
文献类型：
--
作者：
Khan, Safi U.;Talluri, Swapna;Krasuski, Richard
背景资料：他汀类药物、依折麦布联合或不联合他汀类药物和前蛋白转化酶枯草杆菌蛋白酶-kexin 9型（PCSK 9）抑制剂的比较效果尚未评估。设计：进行贝叶斯网络荟萃分析以比较治疗组。方法：使用MEDLINE、EMBASE和CENTRAL选择39个随机对照试验（开始-2017年9月）。在189，116例患者的网络荟萃分析中，PCSK 9抑制剂被评为预防主要心血管不良事件的最佳治疗（累积等级曲线下表面（SUCRA），85%），心肌梗死（SUCRA，84%）和中风（SUCRA，80%）。与依折麦布他汀相比，PCSK 9抑制剂降低了主要心血管不良事件的风险（比值比（OR）：0.72; 95%可信区间（CrI）：0.55-0.95;推荐评估、发展和评价分级（GRADE）标准：中度），他汀类药物（OR：0.78; 95% CrI：0.62-0.97;等级：中度）和安慰剂（OR：0.63; 95% CrI：0.49-0.79;等级：高）。在二级预防试验中，PCSK 9抑制剂在减少主要不良心血管事件方面始终上级各组（SUCRA，95%）。他汀类药物的全因死亡率（SUCRA，82%）和心血管死亡率（SUCRA，84%）最低。与安慰剂相比，他汀类药物降低了全因死亡率（OR：0.88; 95%CrI：0.83-0.94; GRADE：中度）和心血管死亡率（OR：0.84; 95%CrI：0.77-0.90; GRADE：高）的风险。对于心血管死亡率，PCSK 9抑制剂被列为第二好的治疗（SUCRA，78%），其次是依折麦布他汀（SUCRA，50%）。结论：PCSK 9抑制剂被列为减少主要不良心血管事件，心肌梗死和卒中的最有效治疗，没有重大的安全性问题。他汀类药物被列为降低死亡率的最有效疗法。
Background: The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed.Design: Bayesian network meta-analysis was conducted to compare treatment groups.Methods: Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017).Results: In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibethornstatin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49-0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83-0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77-0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibethornstatin (SUCRA, 50%).Conclusion: PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.