Department of Cardiology, Sorbonne Université, ACTION study group, UMR_S 1166, Institut de Cardiologie, Pitié Salpêtrière Hospital (AP-HP), Paris, France.
Department of Interventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eur Heart J Cardiovasc Pharmacother. 2021 May 23;7(3):225-235. doi: 10.1093/ehjcvp/pvaa024.
Although alirocumab and evolocumab have both been associated with improved outcomes in patients with dyslipidaemia or established atherosclerotic cardiovascular disease, data on their respective performances are scarce. This study aimed at providing an indirect comparison of the efficacy and safety of alirocumab vs. evolocumab.
We conducted a systematic review and network meta-analysis of randomized trials comparing alirocumab or evolocumab to placebo with consistent background lipid-lowering therapy up to November 2018. We estimated the relative risk (RR) and the 95% confidence intervals (CIs) using fixed-effect model in a frequentist pairwise and network meta-analytic approach. A total of 30 trials, enrolling 59 026 patients were included. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. Compared with evolocumab, alirocumab was associated with a significant reduction in all-cause death (RR 0.80, 95% CI 0.66-0.97) but not in cardiovascular death (RR 0.83, 95% CI 0.65-1.05). This study did not find any significant differences in myocardial infarction (RR 1.15, 95% CI 0.99-1.34), stroke (RR 0.96, 95% CI 0.71-1.28), or coronary revascularization (RR 1.13, 95% CI 0.99-1.29) between the two agents. Alirocumab was associated with a 27% increased risk of injection site reaction compared to evolocumab; however, no significant differences were found in terms of treatment discontinuations, systemic allergic reaction, neurocognitive events, ophthalmologic events, or new-onset of or worsening of pre-existing diabetes.
Alirocumab and evolocumab share a similar safety profile except for injection site reaction. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to the heterogeneity of the studied populations treated with the two drugs.
尽管阿利西尤单抗和依洛尤单抗均与血脂异常或已确诊的动脉粥样硬化性心血管疾病患者的改善结局相关，但关于这两种药物各自疗效的数据却很少。本研究旨在提供阿利西尤单抗与依洛尤单抗疗效和安全性的间接比较。
我们对截至 2018 年 11 月比较阿利西尤单抗或依洛尤单抗与安慰剂联合常规降脂治疗的随机试验进行了系统评价和网络荟萃分析。我们采用固定效应模型在频繁主义的两两和网络荟萃分析方法中估计相对风险（RR）和 95%置信区间（CI）。共纳入 30 项试验，共纳入 59026 例患者。评估阿利西尤单抗和依洛尤单抗的试验纳入标准差异显著。与依洛尤单抗相比，阿利西尤单抗显著降低全因死亡率（RR 0.80，95%CI 0.66-0.97），但不降低心血管死亡率（RR 0.83，95%CI 0.65-1.05）。本研究未发现两种药物在心肌梗死（RR 1.15，95%CI 0.99-1.34）、卒中和冠状动脉血运重建（RR 1.13，95%CI 0.99-1.29）方面存在显著差异。与依洛尤单抗相比，阿利西尤单抗发生注射部位反应的风险增加 27%；然而，在治疗中断、全身性过敏反应、神经认知事件、眼科事件或新发或恶化的原有糖尿病方面，两种药物之间无显著差异。
阿利西尤单抗和依洛尤单抗具有相似的安全性特征，除了注射部位反应。除全因死亡率外，在疗效终点方面未观察到显著差异，这可能与两种药物治疗的研究人群异质性有关。
