英克西兰对动脉粥样硬化性心血管疾病患者的影响：ORION-10和ORION-11随机试验的汇总分析

Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials.

作者信息

Wright R Scott, Ray Kausik K, Landmesser Ulf, Koenig Wolfgang, Raal Frederick J, Leiter Lawrence A, Conde Lorena Garcia, Han Jackie, Schwartz Gregory G

机构信息

Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN, USA.

Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, UK.

出版信息

Mayo Clin Proc. 2024 Jul 5. doi: 10.1016/j.mayocp.2024.03.025.

DOI:10.1016/j.mayocp.2024.03.025

PMID:39093262

Abstract

OBJECTIVE

To evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) from ORION-10 and ORION-11 stratified by key patient characteristics.

PATIENTS AND METHODS

Participants were randomized 1:1 to receive 300 mg inclisiran sodium (284 mg inclisiran) or placebo on days 1, 90, 270, and 450, alongside background lipid-lowering therapy. This pooled, post hoc analysis stratified participants with ASCVD by sex, age, race, kidney function, body mass index, and glycemic status. Co-primary endpoints were percentage changes in low-density lipoprotein cholesterol (LDL-C) from baseline to day 510, and after day 90 and up to day 540 (time-adjusted). LDL-C goal attainment and safety were also assessed.

RESULTS

This analysis of 2975 participants included: female, n=827; Black, n=213; 75 years of age or older, n=458; obese, n=1474; diabetes, n=1182; and moderate-to-severe chronic kidney disease, n=538. Mean baseline LDL-C levels in the total ASCVD population were balanced between treatment arms (inclisiran, 103.4 mg/dL; placebo, 102.0 mg/dL). With inclisiran, mean placebo-corrected percentage changes in LDL-C from baseline were -51.5% (95% CI, -54.0% to -49.0%) and -52.1% (95% CI, -53.9% to -50.4%) to day 510 and day 540 (time-adjusted), respectively; this was consistent across subgroups. LDL-C less than 55 mg/dL at 1 or more visits was reached by 87.6% of participants receiving inclisiran. The inclisiran safety profile was consistent across subgroups.

CONCLUSION

Twice-yearly inclisiran (after initial and 3-month doses) was well-tolerated and provided significant, consistent LDL-C reductions for up to 18 months in participants with ASCVD independent of key patient characteristics (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]; NCT03399370 and ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]; NCT03400800).

摘要

目的

评估在ORION - 10和ORION - 11研究中，根据关键患者特征分层的动脉粥样硬化性心血管疾病（ASCVD）参与者中，inclisiran的疗效、安全性和耐受性。

患者和方法

参与者按1:1随机分组，在第1天、90天、270天和450天接受300毫克inclisiran钠（284毫克inclisiran）或安慰剂，并接受背景降脂治疗。这项汇总的事后分析根据性别、年龄、种族、肾功能、体重指数和血糖状态，对患有ASCVD的参与者进行分层。共同主要终点是从基线到第510天以及第90天后至第540天（时间调整后）低密度脂蛋白胆固醇（LDL - C）的百分比变化。还评估了LDL - C目标达成情况和安全性。

结果

对2975名参与者的分析包括：女性，n = 827；黑人，n = 213；75岁及以上，n = 458；肥胖，n = 1474；糖尿病，n = 1182；中度至重度慢性肾脏病，n = 538。在整个ASCVD人群中，各治疗组的平均基线LDL - C水平相当（inclisiran组为103.4毫克/分升；安慰剂组为102.0毫克/分升）。使用inclisiran时，从基线到第510天和第540天（时间调整后），LDL - C相对于安慰剂的平均校正百分比变化分别为 - 51.5%（95%CI， - 54.0%至 - 49.0%）和 - 52.1%（95%CI， - 53.9%至 - 50.4%）；各亚组情况一致。接受inclisiran的参与者中有87.6%在1次或更多次就诊时LDL - C低于55毫克/分升。inclisiran的安全性在各亚组中一致。

结论

对于患有ASCVD的参与者，每年两次注射inclisiran（初始剂量和3个月剂量后）耐受性良好，在长达18个月的时间里能显著且持续降低LDL - C，且不受关键患者特征影响（ORION - 10 [动脉粥样硬化性心血管疾病和低密度脂蛋白胆固醇升高参与者的inclisiran研究]；NCT03399370和ORION - 11 [ASCVD或ASCVD风险等同物及低密度脂蛋白胆固醇升高受试者的inclisiran研究]；NCT03400800）。