Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Institute for Translational Medicine and Therapeutics, Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Orphanet J Rare Dis. 2018 Jun 20;13(1):96. doi: 10.1186/s13023-018-0841-3.
Homozygous familial hypercholesterolaemia (HoFH) is characterized by a markedly increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide reduces low-density lipoprotein cholesterol (LDL-C) levels; however, the probable impact on LDL-C goals and CV events is unknown.
We used data collected in the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) to evaluate achievement of European Atherosclerosis Society (EAS) LDL-C targets. We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306).
Twenty-nine patients were included in the phase 3 study. During the first 26 weeks, 15 (51%) and eight (28%) reached LDL-C targets of 100 mg/dL and 70 mg/dL, respectively, at least once. Fourteen (74%) and 11 (58%) of the 19 patients who remained in the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the entire study period. Only two MACE were reported in the lomitapide trials (one cardiac death and one coronary artery bypass graft (CABG)) - equivalent to 1.7 events per 1000 patient months of treatment. MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of HoFH patients pre- and post-mipomersen, and receiving evolocumab. On treatment LDL-C levels were 166, 331 and 286 mg/dL for lomitapide, mipomersen and evolocumab, respectively.
Approximately three quarters and half of patients who took lomitapide for at least 2 years reached LDL-C goals of 100 mg/dL and 70 mg/dL, respectively. There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further.
NCT00730236 (registered 8 Aug 2008) and NCT00943306 (registered 22 July 2009).
家族性高胆固醇血症（HoFH）的特征是过早发生心血管（CV）事件和心脏死亡的风险明显增加。洛美他派可降低低密度脂蛋白胆固醇（LDL-C）水平；然而，其对 LDL-C 目标和 CV 事件的可能影响尚不清楚。
我们使用 lomitapide 关键性 3 期研究（NCT00730236）的前 26 周收集的数据来评估欧洲动脉粥样硬化学会（EAS）LDL-C 目标的达标情况。我们使用其他 HoFH 患者队列报告的主要不良心血管事件（MACE）发生率的公开可用数据，比较 lomitapide 扩展试验（NCT00943306）中接受等效患者年暴露（98）的事件发生率。
29 名患者被纳入 3 期研究。在前 26 周内，15 名（51%）和 8 名（28%）患者至少有一次达到了 100mg/dL 和 70mg/dL 的 LDL-C 目标。在第 126 周后继续进入扩展研究的 19 名患者中，14 名（74%）和 11 名（58%）患者在整个研究期间至少有一次达到了 100mg/dL 和 70mg/dL 的 LDL-C 目标。在 lomitapide 试验中仅报告了 2 例 MACE（1 例心脏死亡和 1 例冠状动脉旁路移植术（CABG）），相当于每 1000 患者治疗月治疗有 1.7 例事件。在 mipomersen 治疗前和治疗后的 HoFH 患者队列以及接受 evolocumab 的患者队列中，MACE 发生率分别为每 1000 患者治疗月 21.7、9.5 和 1.8 例。服用 lomitapide、mipomersen 和 evolocumab 的患者治疗 LDL-C 水平分别为 166、331 和 286mg/dL。
接受 lomitapide 治疗至少 2 年的患者中，约有 3/4 和一半分别达到了 LDL-C 目标的 100mg/dL 和 70mg/dL。与 mipomersen 队列在开始 mipomersen 治疗前相比，接受 lomitapide、mipomersen 或 evolocumab 治疗的患者每 1000 患者治疗月的主要 CV 事件更少。这些结果支持这样一种假设，即新型降脂疗法通过进一步降低 LDL-C 水平，可能降低 HoFH 患者的 CV 事件。
NCT00730236（2008 年 8 月 8 日注册）和 NCT00943306（2009 年 7 月 22 日注册）。
