Inclisiran-based treatment strategy in hypercholesterolaemia: the VICTORION-difference trial.

The European Society of Cardiology guidelines recommend combination treatment to achieve CV risk-based LDL-C treatment goals.

欧洲心脏病学会指南推荐联合治疗以实现基于心血管风险的LDL-C治疗目标。

Inclisiran, a small interfering ribonucleic acid (siRNA) that targets hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA, can provide sustained and effective LDL-C reduction.

Inclisiran是一种针对肝脏前体蛋白转化酶枯草杆菌/嗜热脂肪杆菌型9（PCSK9）信使RNA的小干扰核糖核酸（siRNA），可以提供持续且有效的低密度脂蛋白胆固醇（LDL-C）降低。

Methods

VICTORION-Difference, a phase 4 double-blind, placebo-controlledrandomized clinical trial included adults with hypercholesterolaemia at high- or very high CV risk.

VICTORION-Difference是一项第四阶段的双盲、安慰剂对照的随机临床试验，纳入了高胆固醇血症且具有高或极高心血管风险的成年人。

Participants were randomized 1:1 to receive inclisiran sodium (300 mg subcutaneous injections; equivalent to 284 mg inclisiran) or placebo together with individually optimized lipid-lowering therapy (ioLLT), including up-titration with rosuvastatin (open-label) until either their individual LDL-C goal or maximally tolerated statin dose (open-label rosuvastatin) was achieved.

参与者按1:1的比例随机接受inclisiran钠（300 mg皮下注射；相当于284 mg的inclisiran）或安慰剂，同时接受个体化的降脂治疗（ioLLT），包括使用rosuvastatin（开放标签）进行剂量上调，直到达到个体的LDL-C目标或最大耐受的他汀剂量（开放标签的rosuvastatin）为止。

The primary objective was assessment of LDL-C goal achievement at Day 90.

主要目标是评估第90天时达到LDL-C目标的情况。

Key secondary objectives were muscle-related adverse events (MRAEs) and mean LDL-C reduction.

主要次要终点是肌肉相关不良事件（MRAEs）和平均LDL-C降低。

Overall, 1770 individuals (mean age, 63.7 years) were randomized to receive inclisiran (n = 898) or ioLLT (n = 872).

总体而言，1770名个体（平均年龄63.7岁）被随机分配接受inclisiran治疗（n = 898）或ioLLT治疗（n = 872）。

At Day 90, a significantly higher proportion of participants receiving inclisiran vs. ioLLT achieved their individual LDL-C goals [84.9% vs 31.0%; odds ratio (OR) 12.09, P < .001].

在第90天，接受inclisiran治疗的参与者与接受ioLLT治疗的参与者相比，达到个体低密度脂蛋白胆固醇(LDL-C)目标的比例显著更高[84.9%对比31.0%；优势比(OR)为12.09，P < .001]。

The mean percentage reduction in LDL-C from baseline to Day 360 was -59.5% and -24.3% in the inclisiran and ioLLT arms, respectively [least squares mean treatment difference (LSMTD) = -35.14%, P < .001].

从基线到第360天，inclisiran组和ioLLT组的LDL-C平均百分比降低分别为-59.5%和-24.3%[最小二乘均值治疗差异(LSMTD) = -35.14%，P < .001]。

Fewer participants receiving inclisiran vs ioLLT reported a MRAE (11.9% vs 19.2%; OR 0.57, P < .001).

接受inclisiran治疗的参与者报告的MRAE（主要不良肾事件）比接受ioLLT治疗的参与者少（11.9% vs 19.2%；OR 0.57, P < .001）。

The mean reduction in Short Form-Brief Pain Inventory pain severity and interference scores favoured inclisiran over ioLLT (LSMTD = -0.11, P = .039; LSMTD = -0.11, P = .029, respectively).

Short Form-Brief Pain Inventory疼痛严重程度和干扰评分的平均降低值倾向于inclisiran优于ioLLT（LSMTD = -0.11, P = .039; LSMTD = -0.11, P = .029，分别）。

No new safety concerns were identified.

未发现新的安全问题。

Results

Overall, 1770 individuals (mean age, 63.7 years) were randomized to receive inclisiran (n=898) or ioLLT (n=872).

总体而言，1770名受试者（平均年龄63.7岁）被随机分配接受inclisiran治疗（n=898）或ioLLT治疗（n=872）。

At Day 90, a significantly higher proportion of participants receiving inclisiran vs. ioLLT achieved their individual LDL-C goals (84.9% vs. 31.0%; odds ratio [OR] 12.09, p<0.001).

在第90天，接受inclisiran治疗的参与者与接受ioLLT治疗的参与者相比，达到个体低密度脂蛋白胆固醇(LDL-C)目标的比例显著更高(84.9% vs. 31.0%; 比值比[OR] 12.09, p<0.001)。

The mean percentage reduction in LDL-C from baseline to Day 360 was -59.5% and -24.3% in the inclisiran and ioLLT arms, respectively (least squares mean treatment difference [LSMTD]=-35.14%, p<0.001).

从基线到第360天，inclisiran组和ioLLT组的LDL-C平均百分比降低分别为-59.5%和-24.3%（最小二乘均值治疗差异[LSMTD]=-35.14%，p<0.001）。

Fewer participants receiving inclisiran vs. ioLLT reported a MRAE (11.9% vs. 19.2%; OR 0.57, p<0.001).

接受inclisiran治疗的参与者报告主要不良肾事件(MRAE)的比例低于接受ioLLT治疗的参与者(11.9% vs. 19.2%; OR 0.57, p<0.001)。

The mean reduction in Short Form-Brief Pain Inventory pain severity and interference scores favoured inclisiran over ioLLT (LSMTD=-0.11, p=0.039; LSMTD=-0.11, p=0.029, respectively).

与ioLLT相比，inclisiran在减少短版简明疼痛评估量表(SF-BPI)疼痛严重程度和干扰评分的平均值方面更为有利(LSMTD=-0.11, p=0.039; LSMTD=-0.11, p=0.029，分别)。

No new safety concerns were identified.

未发现新的安全问题。

Conclusions

An inclisiran-based treatment strategy was superior to ioLLT in LDL-C goal achievement, delivering early and sustained LDL-C reduction, with fewer MRAEs in individuals with hypercholesterolaemia.

基于inclisiran的治疗策略在达到低密度脂蛋白胆固醇（LDL-C）目标方面优于离子低密度脂蛋白治疗（ioLLT），实现了早期和持续的LDL-C降低，并且在高胆固醇患者中不良反应事件更少。