Inclisiran用于既往有心肌梗死患者：ORION-10和ORION-11 3期随机试验的事后汇总分析。

Inclisiran in patients with prior myocardial infarction: A post hoc pooled analysis of the ORION-10 and ORION-11 Phase 3 randomised trials.

作者信息

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

机构信息

Department of Cardiology, Angiology, and Intensive Care Medicine, Deutsches Herzzentrum Charité; Charité Universitätsmedizin Berlin, Berlin Institute of Health (BIH), DZHK, Partner Site Berlin, Berlin, Germany.

Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.

出版信息

Atherosclerosis. 2023 Dec;386:117354. doi: 10.1016/j.atherosclerosis.2023.117354. Epub 2023 Oct 18.

DOI:10.1016/j.atherosclerosis.2023.117354

PMID:38016401

Abstract

BACKGROUND AND AIMS

Among patients with prior myocardial infarction (MI), the risk of future ischaemic cardiovascular events is increased, and intensive lipid-lowering therapy (LLT) is indicated to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Here, the efficacy and safety of inclisiran, a small interfering ribonucleic acid, were evaluated in patients with or without prior MI from the pooled ORION-10 and ORION-11 Phase 3 trials.

METHODS

Patients (n = 2636) were randomised 1:1 to receive 284 mg inclisiran (300 mg inclisiran sodium) or placebo on Day 1, Day 90, and 6-monthly thereafter over 18 months, along with background oral LLT, including statins. Of these, 1643 (62.3%) patients had an MI prior to randomisation, stratified as recent (>3 months to <1 year) or remote (≥1 year), and 993 (37.7%) patients were without a prior MI. The percentage change in LDL-C from baseline and safety were assessed.

RESULTS

Baseline characteristics were well balanced across the treatment arms and MI strata. The mean (95% confidence interval) placebo-corrected LDL-C reductions from baseline to Day 510 with inclisiran were 52.6% (40.1, 65.1), 50.4% (47.0, 53.8), and 51.6% (47.4, 55.9) for recent, remote, and no prior MI, respectively. Corresponding time-adjusted LDL-C reductions were 50.0% (41.4, 58.7), 52.2% (49.8, 54.7), and 51.2% (48.1, 54.2). In each MI stratum, treatment-emergent adverse events (TEAEs) at the injection site (all mild to moderate) were observed more in inclisiran-treated patients than placebo, without an excess of other TEAEs.

CONCLUSIONS

Inclisiran provided effective and consistent LDL-C lowering, irrespective of MI status.

摘要

背景与目的

在既往有心肌梗死（MI）的患者中，未来发生缺血性心血管事件的风险会增加，因此需要强化降脂治疗（LLT）以实现指南推荐的低密度脂蛋白胆固醇（LDL-C）目标。在此，我们在ORION - 10和ORION - 11这两项3期试验的汇总数据中，评估了小干扰核糖核酸英克西兰在有或无既往心肌梗死患者中的疗效和安全性。

方法

2636例患者按1:1随机分组，在第1天、第90天以及之后每6个月接受一次284毫克英克西兰（300毫克英克西兰钠）或安慰剂注射，为期18个月，同时接受包括他汀类药物在内的背景口服降脂治疗。其中，1643例（62.3%）患者在随机分组前有心肌梗死，分为近期（>3个月至<1年）或远期（≥1年），993例（37.7%）患者无既往心肌梗死。评估LDL-C相对于基线的变化百分比和安全性。

结果

各治疗组和心肌梗死分层的基线特征均衡。从基线到第510天，英克西兰治疗组经安慰剂校正后的LDL-C平均降低值（95%置信区间），近期心肌梗死患者为52.6%（40.1，65.1），远期心肌梗死患者为50.4%（47.0，53.8），无既往心肌梗死患者为51.6%（47.4，55.9）。相应的时间校正LDL-C降低值分别为50.0%（41.4，58.7）、52.2%（49.8，54.7）和51.2%（48.1，54.2）。在每个心肌梗死分层中，英克西兰治疗组患者注射部位出现的治疗中出现的不良事件（TEAE，均为轻至中度）比安慰剂组更多，但其他TEAE并未增加。