Background

The 24-week randomized, double-blind ODYSSEY ALTERNATIVE trial (NCT01709513) demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 inhibitor alirocumab vs ezetimibe in statin-intolerant patients, with significantly fewer skeletal muscle events (SMEs; 32.5%) vs atorvastatin (46.0%; hazard ratio: 0.61, 95% confidence interval: 0.38 to 0.99, P = .042).

Objective

ALTERNATIVE participants could enter an open-label treatment period (OLTP) for assessment of long-term safety.

Methods

Two hundred and eighty one patients entered the OLTP; 93.7%, 84.0%, and 92.9% of patients who received atorvastatin, ezetimibe, and alirocumab, respectively, during double-blind treatment, including 216 patients (76.9%) who completed double-blind treatment, as well as patients who either prematurely discontinued treatment due to SME (n = 51 [18.1%]) or other reasons (n = 14 [5.0%]) but completed week 24 assessments. All patients in the OLTP received alirocumab (75 or 150 mg every 2 weeks based on investigator decision) for ∼3 years or until commercial availability, whichever came first.

Results

SMEs were reported by 38.4% of patients in the OLTP. Safety results from the OLTP were similar to those of the alirocumab group in the double-blind period, except for a lower rate of discontinuations due to SMEs observed with alirocumab in the OLTP (3.2% vs 15.9% in the double-blind period). At OLTP week 8, mean LDL-C reduction from baseline (=week 0 of double-blind period) was 52.0%, with reductions sustained through to the end-of-treatment visits (55.4% and 53.7% reduction at weeks 100 and 148, respectively).

Conclusions

In this population of statin-intolerant patients, alirocumab was well tolerated and produced durable LDL-C reductions over 3 years.

中文翻译：

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Alirocumab在他汀类药物耐受不良患者中超过3年的疗效和安全性：ODYSSEY ALTERNATIVE试验的开放标签治疗期。

背景

这项为期24周的随机，双盲ODYSSEY ALTERNATIVE试验（NCT01709513）表明，他汀类药物耐受患者中PCSK9抑制剂alirocumab与ezetimibe显着降低了低密度脂蛋白胆固醇（LDL-C），骨骼肌事件（SMEs; 32.5％）与阿托伐他汀（46.0％;危险比： 0.61，95 ％置信区间：0.38至0.99，P = .042）。

目的

替代参与者可以进入开放治疗期（OLTP）以评估长期安全性。

方法

281例患者进入OLTP。在双盲治疗期间分别接受阿托伐他汀，依泽替米贝和阿罗单抗的患者的93.7％，84.0％和92.9％，包括完成双盲治疗的216例患者（76.9％）以及过早停用的患者因中小型企业（n = 51 [18.1％]）或其他原因（n = 14 [5.0％]）而进行的治疗，但完成了第24周的评估。OLTP中的所有患者均接受alirocumab（根据研究者的决定，每2周75或150 mg）〜3年或直到商业可得为止，以先到者为准。

结果

OLTP中有38.4％的患者报告了SME。在双盲期间，OLTP的安全性结果与alirocumab组相似，不同之处在于，在OLTP中使用alirocumab观察到的中小企业导致中止率较低（双盲期间为3.2％对15.9％）。在OLTP第8周，与基线（=双盲期的第0周）相比，LDL-C的平均减少量为52.0％，直至治疗结束就诊期间均持续减少（在第100和148周时分别减少55.4％和53.7％） ， 分别）。

结论

在不接受他汀类药物治疗的人群中，alirocumab的耐受性良好，并在3年​​内产生了持久的LDL-C降低。