West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China.
West China Brain Research Centre, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Cardiovasc Diabetol. 2022 Jun 15;21(1):107. doi: 10.1186/s12933-022-01542-4.
The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors.
Several databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events.
Overall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72-0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04-1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90-0.99).
In consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.
美国食品药品监督管理局已批准前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂用于治疗血脂异常。然而，缺乏高危心血管事件患者使用 PCSK9 抑制剂针对 PCSK9 进行二级预防的最佳证据。因此，本研究旨在评估不同类型的 PCSK9 抑制剂的获益和安全性。
从建库到 2022 年 3 月 30 日，我们在 Cochrane 中央、Ovid Medline 和 Ovid Embase 等多个数据库中进行了无语言限制的检索。我们确定了比较 PCSK9 抑制剂与安慰剂或依折麦布用于他汀类药物背景治疗患者二级预防心血管事件的随机对照试验（RCT）。主要疗效结局为全因死亡率。主要安全性结局为严重不良事件。
共纳入 9 项试验，总计 54311 例患者。评估了 3 种 PCSK9 抑制剂。与对照组相比，使用阿利西尤单抗可降低全因死亡率（RR 0.83，95%CrI 0.72-0.95）。此外，与阿利西尤单抗相比，依洛尤单抗可增加全因死亡率（RR 1.26，95%CrI 1.04-1.52）。我们还发现，与阿利西尤单抗相比，阿利西尤单抗可降低严重不良事件的风险（RR 0.94，95%CrI 0.90-0.99）。
鉴于 PCSK9 单克隆抗体和inclisiran 均可使患者达到 LDL-C 目标，本荟萃分析的结果表明，阿利西尤单抗可能在全因死亡率方面提供最佳获益，同时严重不良事件风险相对较低，而依洛尤单抗可能在高危心血管事件患者的二级预防中提供最佳获益，心肌梗死。需要进行更多具有更长随访时间和更高方法学质量的头对头试验，以帮助为这些患者的管理提供后续指南。
