Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials.

Mean percentage LDL cholesterol reduction from baseline was around 50% regardless of eGFR in phase 3 trials.

在第三阶段试验中，无论eGFR如何，从基线开始的LDL胆固醇平均降低百分比约为50%。

Inclisiran showed sustained and effective LDL cholesterol-lowering in patients across various levels of eGFR values, without new safety findings.

Inclisiran在不同eGFR值的患者中显示出持续有效的降低LDL胆固醇效果，且未发现新的安全问题。

Background

Lowering LDL cholesterol reduces the risk of atherosclerotic cardiovascular disease in patients with CKD.

降低LDL胆固醇可以降低慢性肾脏病患者动脉粥样硬化性心血管疾病的风险。

The efficacy and safety of inclisiran versus placebo in patients without and with CKD were investigated in a post hoc pooled analysis of three phase 3 trials (ORION-9, ORION-10, and ORION-11).

在对三项第三阶段试验（ORION-9、ORION-10和ORION-11）的事后汇总分析中，研究了在没有和有慢性肾脏病（CKD）的患者中，inclisiran与安慰剂的疗效和安全性。

Methods

Patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease or its risk equivalent, and elevated LDL cholesterol were randomized 1:1 to subcutaneous inclisiran or placebo on days 1 and 90 and every 6 months thereafter for 540 days.

被随机分配为1:1的皮下注射inclisiran或安慰剂的患者，包括杂合子家族性高胆固醇血症患者、动脉粥样硬化性心血管疾病或其风险等价患者，以及LDL胆固醇升高的患者，在第1天和第90天以及之后每6个月进行一次，持续540天。

Patients were stratified based on baseline eGFR (by CKD Epidemiology Collaboration equation): ≥90, 60 to <90, 45 to <60, and 15 to <45 ml/min per 1.73 m 2 .

患者根据基线eGFR（使用CKD流行病学合作方程）进行分层：≥90、60至<90、45至<60和15至<45 ml/min per 1.73 m2。

Coprimary end points were percentage change in LDL cholesterol at day 510 and time-adjusted percentage change after day 90 and through day 540.

主要终点是第510天LDL胆固醇的百分比变化以及第90天后至第540天的时间调整百分比变化。

Safety was also evaluated.

安全性也得到了评估。

Results

Of 3660 patients, 1610 (44%) had eGFR ≥90, 1608 (44%) 60 to <90, 300 (8%) 45 to <60, and 142 (4%) 15 to <45 ml/min per 1.73 m 2 .

在3660名患者中，有1610名（44%）的eGFR（估算肾小球滤过率）≥90，1608名（44%）的eGFR在60到<90之间，300名（8%）的eGFR在45到<60之间，以及142名（4%）的eGFR在15到<45 ml/min per 1.73 m2之间。

The mean (95% confidence interval) placebo-corrected percentage changes in LDL cholesterol from baseline at day 510 in patients with eGFR ≥90, 60 to <90, 45 to <60, and 15 to <45 ml/min per 1.73 m 2 were -49.9% (-53.2 to -46.6), -51.2% (-54.4 to -48.0), -54.7% (-62.5 to -47.0), and -44.7% (-57.6 to -31.8), respectively ( P < 0.001); the corresponding mean (95% confidence interval) time-adjusted placebo-corrected percentage changes in LDL cholesterol from baseline after day 90 through day 540 were -48.4% (-50.8 to -46.1), -51.8% (-54.2 to -49.4), -55.6% (-61.0 to -50.2), and -50.4% (-59.3 to -41.5; each P < 0.001).

在基线至第510天时，eGFR ≥90, 60至<90, 45至<60, 和15至<45 ml/min per 1.73 m^2的患者中，安慰剂校正的LDL胆固醇平均百分比变化（95%置信区间）分别为-49.9%（-53.2至-46.6%），-51.2%（-54.4至-48.0%），-54.7%（-62.5至-47.0%），和-44.7%（-57.6至-31.8%）（每个P < 0.001）；相应地，在第90天至第540天期间，从基线开始的时间调整后的安慰剂校正的LDL胆固醇平均百分比变化（95%置信区间）分别为-48.4%（-50.8至-46.1%），-51.8%（-54.2至-49.4%），-55.6%（-61.0至-50.2%），和-50.4%（-59.3至-41.5%；每个P < 0.001）。

Significant decreases in total cholesterol, apolipoprotein B, non-HDL cholesterol, and lipoprotein(a) occurred in all eGFR groups.

所有eGFR组中，总胆固醇、载脂蛋白B、非HDL胆固醇和脂蛋白(a)均有显著下降。

Inclisiran was well tolerated without new safety findings.

Inclisiran耐受性良好，未发现新的安全问题。

Conclusions

Inclisiran demonstrated sustained and effective LDL cholesterol reduction in patients with or at risk of atherosclerotic cardiovascular disease, regardless of baseline eGFR as low as 15 ml/min per 1.73 m 2 , without new safety findings.

Inclisiran在动脉粥样硬化性心血管疾病患者或高风险患者中显示出持续且有效的低密度脂蛋白胆固醇降低效果，无论基线eGFR低至15 ml/min per 1.73 m2，且未发现新的安全问题。

clinical_trial_registry_name_and

ClinicalTrials.gov, ORION-9 ( NCT03397121 ), ORION-10 ( NCT03399370 ), and ORION-11 ( NCT03400800 ).

临床试验注册中心，ORION-9 (NCT03397121)，ORION-10 (NCT03399370)，以及ORION-11 (NCT03400800)。