Background

Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease.

Objective

We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status.

Methods

Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non–familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status.

Results

Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups.

Conclusions

In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.

中文翻译：

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依年龄，吸烟状况和高血压而定的alirocumab的治疗效果：来自10项ODYSSEY随机研究的汇总分析。

背景

年龄，吸烟，高胆固醇血症和高血压是动脉粥样硬化性心血管疾病的主要危险因素。

客观的

我们检查了alirocumab对低密度脂蛋白胆固醇（LDL-C）的影响是否根据年龄，高血压或吸烟状况而有所不同。

方法

数据来自10项ODYSSEY 3期随机试验（持续24-104周），收集了4983例杂合性家族性高胆固醇血症（FH）或非家族性高胆固醇血症（阿罗洛单抗为3188，对照组为1795 [依泽替米贝为620，安慰剂为1175]） ）。大多数参与者都接受了最大耐受他汀类药物治疗。在8个试验中，如果在第8周未达到基于风险的预定义LDL-C目标（≥70 mg / dL，在非常高的心血管疾病中），则alirocumab剂量从第2周的每两周75 mg增加到第12周的150 mg风险；中度或高度心血管风险≥100 mg / dL）。两项试验比较了Alirocumab 150 mg Q2W与安慰剂的比较。在按年龄（<65岁，≥65至<75岁，≥75岁）和基线高血压或吸烟状态分层的亚组中，事后评估了alirocumab的疗效和安全性。

结果

与对照组相比，从基线到第24周，Alirocumab将LDL-C降低了23.7％（75/150 mg vs依泽替米贝+他汀）至65.4％（150 mg vs安慰剂+他汀）。亚组分析证实，年龄，高血压或吸烟状态之间对阿利洛单抗的反应无显着相互作用。Alirocumab与对照组之间出现治疗的不良事件的总体发生率相似。

结论

在这项来自10个试验的汇总分析中，无论高血压或吸烟状况如何，alirocumab导致每个年龄组的LDL-C相对于对照均大幅降低。Alirocumab在所有亚组中均具有良好的耐受性。