Zhao Zonglei, Du Song, Shen Shuxin, Luo Ping, Ding Shoukun, Wang Guanggong, Wang Lixia
Department of Cardiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, China.
Medicine (Baltimore). 2019 Feb;98(6):e14400. doi: 10.1097/MD.0000000000014400.
The comparative efficacy and safety of PCSK9 inhibitors, statins, and ezetimibe to lower lipid levels in patients with hypercholesterolemia remain unknown. We aimed to investigate the benefits and harms of the lipid-lowering agents in these patients.
PubMed, Embase, and the Cochrane Library were searched from January 1, 2000 to June 1, 2018 for relevant randomized controlled trials (RCTs). Frequentist network meta-analysis was used to pool all estimates. Ranking probabilities were used to rank the comparative effects of all drugs against placebo.
Eighty-four RCTs enrolled 246,706 patients were included. Most of the included were assessed as low risk of bias. The probabilities of PCSK9 inhibitors that ranked first in improving lipid outcomes were all 100%. The probability of statins that ranked first in reducing the risk of cardiovascular (CV) events was 60.6%, and the probability of PCSK9 inhibitor was 37.1%, while no significant difference of efficacy in reducing CV events was observed between the 2 agents (odds ratios [OR] 0.98, 95% CI 0.87-1.11). Statin ranked first in reducing all-cause and CV death. Compared with placebo, statins were associated with reduced risks of all-cause (OR 0.90, 95% CI 0.85-0.96) and CV death (OR 0.83, 95% CI 0.75-0.91) while PCSK9 inhibitors and ezetimibe were not. No agents caused adverse events (including neurocognitive events), except that statins therapy significantly increases the levels of alanine aminotransferase (ALT) (OR 1.89, 95% CI 1.42-2.51) and creatine kinase (CK) (OR 1.45, 95% CI 1.09-1.93) and the incidence of diabetes (OR 1.13, 95% CI 1.02-1.26).
PCSK9 inhibitors were the most effective lipid-lowering agents in improving lipid levels. Furthermore, PCSK9 inhibitors achieved similar CV benefits like statins, while PCSK9 inhibitors were not associated with any increased risk of statin-related side-effects. Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.
前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂、他汀类药物和依折麦布降低高胆固醇血症患者血脂水平的相对疗效和安全性尚不清楚。我们旨在研究这些降脂药物在这些患者中的益处和危害。
检索2000年1月1日至2018年6月1日期间的PubMed、Embase和Cochrane图书馆，查找相关随机对照试验（RCT）。采用频率学派网状Meta分析汇总所有估计值。使用排序概率对所有药物与安慰剂的比较效果进行排序。
纳入了84项RCT，共246,706例患者。纳入的大多数研究被评估为低偏倚风险。PCSK9抑制剂在改善血脂结果方面排名第一的概率均为100%。他汀类药物在降低心血管（CV）事件风险方面排名第一的概率为60.6%，PCSK9抑制剂为37.1%，而这两种药物在降低CV事件方面的疗效无显著差异（优势比[OR]0.98，95%CI 0.87-1.11）。他汀类药物在降低全因死亡和CV死亡方面排名第一。与安慰剂相比，他汀类药物可降低全因死亡风险（OR 0.90，95%CI 0.85-0.96）和CV死亡风险（OR 0.83，95%CI 0.75-0.91），而PCSK9抑制剂和依折麦布则不能。除他汀类药物治疗显著增加丙氨酸氨基转移酶（ALT）水平（OR 1.89，95%CI 1.42-2.51）、肌酸激酶（CK）水平（OR 1.45，95%CI 1.09-1.93）以及糖尿病发病率（OR 1.13，95%CI 1.02-1.26）外，没有药物引起不良事件（包括神经认知事件）。
PCSK9抑制剂是改善血脂水平最有效的降脂药物。此外，PCSK9抑制剂在CV获益方面与他汀类药物相似，而PCSK9抑制剂与任何他汀类药物相关副作用风险增加无关。因此，PCSK9抑制剂也可被推荐为高胆固醇血症患者有前景的一线降脂治疗药物，尤其是对他汀类药物不耐受或耐药的患者。
