阿利西尤单抗和依洛尤单抗的疗效与安全性：一项随机对照试验的系统评价和荟萃分析
Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials.
作者信息
Guedeney Paul, Giustino Gennaro, Sorrentino Sabato, Claessen Bimmer E, Camaj Anton, Kalkman Deborah N, Vogel Birgit, Sartori Samantha, De Rosa Salvatore, Baber Usman, Indolfi Ciro, Montalescot Gilles, Dangas George D, Rosenson Robert S, Pocock Stuart J, Mehran Roxana
机构信息
Center for Interventional Cardiovascular Research, The Zena and Michael A. Weiner Cardiovascular Institute, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029, USA.
Department of Cardiology, Sorbonne Université, ACTION Study Group, INSERM UMRS 1166, Institut de Cardiologie (AP-HP), hôpital Pitié Salpêtrière, Paris, France.
出版信息
Eur Heart J. 2022 Feb 12;43(7):e17-e25. doi: 10.1093/eurheartj/ehz430.
AIMS
The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease.
METHODS AND RESULTS
We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin-kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74-0.86; I 2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67-0.89; I 2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78-0.89; I 2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97).
CONCLUSION
Proprotein convertase subtilisin-kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.
目的
阿利西尤单抗或依洛尤单抗降低低密度脂蛋白胆固醇治疗对个体临床疗效和安全性终点的影响仍不明确。我们旨在评估阿利西尤单抗和依洛尤单抗在血脂异常或动脉粥样硬化性心血管疾病患者中的疗效和安全性。
方法与结果
我们对截至2018年3月比较阿利西尤单抗或依洛尤单抗与安慰剂或其他降脂疗法治疗的随机对照试验（RCT）进行了综述。主要疗效终点为全因死亡、心血管死亡、心肌梗死（MI）和中风。我们使用随机效应模型估计风险比（RR）和95%置信区间（CI）。我们纳入了39项RCT，共66478例患者，其中35896例接受前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂治疗（14639例接受阿利西尤单抗治疗，21257例接受依洛尤单抗治疗），30582例接受对照治疗。各试验的平均加权随访时间为2.3年，暴露时间为150617患者年。总体而言，PCSK9抑制对全因死亡和心血管死亡的影响无统计学意义（P分别为0.15和0.34）。与对照组相比，PCSK9抑制剂与较低的MI风险（每100患者年1.49 vs. 1.93；RR 0.80，95%CI 0.74 - 0.86；I² = 0%；P < 0.0001）、缺血性中风风险（每100患者年0.44 vs. 0.58；RR 0.78，95%CI 0.67 - 0.89；I² = 0%；P = 0.0005）和冠状动脉血运重建风险（每100患者年2.16 vs. 2.64；RR 0.83，95%CI 0.78 - 0.89；I² = 0%；P < 0.0001）相关。使用这些PCSK9抑制剂与神经认知不良事件风险增加（P = 0.91）、肝酶升高（P = 0.34）、横纹肌溶解（P = 0.58）或新发糖尿病（P = 0.97）无关。
结论
阿利西尤单抗或依洛尤单抗抑制PCSK9与较低的MI、中风和冠状动脉血运重建风险相关，且安全性良好。
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