Cicarrone Center for the Prevention of Cardiovascular Disease Johns Hopkins University School of Medicine Baltimore MD.
Amgen Ltd Cambridge UK.
J Am Heart Assoc. 2022 Sep 20;11(18):e025551. doi: 10.1161/JAHA.122.025551. Epub 2022 Sep 8.
Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.
背景 降低低密度脂蛋白胆固醇 (LDL-C) 水平可减少主要心血管事件，因此建议心血管风险升高的患者采用这种治疗方法。然而，目前的指南建议，通常情况下，大剂量他汀类药物治疗仍不足以降低 LDL-C 水平。在这种情况下，可以补充非他汀类降脂治疗。
方法和结果 对联合最大耐受剂量他汀类药物治疗的非他汀类降脂治疗的随机对照试验进行了系统的文献复习和网络荟萃分析，包括他汀类药物不耐受的患者。主要目的是评估非他汀类降脂治疗在第 12 周降低 LDL-C 水平的相对疗效。次要目标包括：第 24 周 LDL-C 水平的降低和第 12 周非高密度脂蛋白胆固醇和载脂蛋白 B 的变化。主要网络荟萃分析共纳入 48 项随机对照试验。与安慰剂相比，所有非他汀类药物均能显著降低 LDL-C 水平，无论背景治疗如何。在第 12 周，依洛尤单抗，140mg，每 2 周 1 次（Q2W）/420mg，每月 1 次，和阿利西尤单抗，150mg Q2W，是最有效的治疗方案，其次是阿利西尤单抗，75mg Q2W，阿利西尤单抗，每月 1 次 300mg，inclisiran，贝美前列素/依折麦布固定剂量复方制剂和依折麦布和贝美前列素作为单药治疗。主要终点结果在第 24 周时基本一致，其他脂质终点在第 12 周时也基本一致。
结论 依洛尤单抗，140mg Q2W/420mg 每月 1 次，和阿利西尤单抗，150mg Q2W，当联合最大耐受剂量他汀类药物降低 LDL-C、非高密度脂蛋白胆固醇和载脂蛋白 B 水平并有助于达到指南推荐的风险分层脂蛋白水平时，是最有效的非他汀类药物治疗方案。
