University of Colorado School of Medicine, Denver, CO.
Sanofi-Aventis Recherche et Développement S.A., Paris, France; Sanofi-Aventis Recherche et Développement S.A., Bridgewater, NJ.
Am Heart J. 2014 Nov;168(5):682-9. doi: 10.1016/j.ahj.2014.07.028. Epub 2014 Aug 7.
Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS.
This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred.
ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
急性冠状动脉综合征（ACS）后，未来心血管事件的风险很高，即使在强化他汀类药物治疗的情况下，也与低密度脂蛋白胆固醇（LDL-C）水平有关。前蛋白转化酶枯草溶菌素/克那霉 9（PCSK9）调节 LDL 受体的表达和 LDL-C 的循环水平。PCSK9 的抗体可显著且持续降低 LDL-C。ODYSSEY 结果试验检验了这样一个假设，即使用完全人源单克隆抗体阿利西尤单抗（一种针对 PCSK9 的抗体）治疗 ACS 后可改善心血管结局。
这项 3 期研究将随机分配约 18000 名患者，在急性心肌梗死或不稳定型心绞痛指数住院后 1 至 12 个月内，每两周接受一次阿利西尤单抗（75-150mg）或匹配安慰剂治疗。符合条件的患者接受阿托伐他汀 40 或 80mg 每日、瑞舒伐他汀 20 或 40mg 每日或最大耐受剂量和批准剂量的一种药物治疗，并符合以下标准之一：LDL-C≥70mg/dL、非高密度脂蛋白胆固醇≥100mg/dL 或载脂蛋白 B≥80mg/dL。主要疗效指标是首次发生冠心病死亡、急性心肌梗死、不稳定型心绞痛住院或缺血性卒中等的时间。预计该试验将持续到发生至少 1613 次主要终点事件，至少随访 2 年，以 90%的概率检测到 15%的风险降低。特别关注的不良事件包括过敏事件和注射部位反应。当达到主要终点事件目标数量的约 50%和 75%时，计划进行中期分析。
ODYSSEY 结果将确定 PCSK9 抗体阿利西尤单抗与强化他汀类药物治疗联合使用是否能降低 ACS 后的心血管发病率和死亡率。
