Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Eur Heart J. 2012 May;33(9):1142-9. doi: 10.1093/eurheartj/ehs023. Epub 2012 Apr 16.
A randomized, double-blind, placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, in patients who are statin intolerant and at high risk for cardiovascular disease (CVD).
Thirty-three subjects, not receiving statin therapy because of statin intolerance, received a weekly subcutaneous dose of 200 mg mipomersen or placebo (2:1 randomization) for 26 weeks. The primary endpoint was per cent change in LDL cholesterol (LDL-c) from the baseline to Week 28. The other efficacy endpoints were per cent change in apoB and lipoprotein a [Lp(a)]. Safety was determined using the incidence of treatment-emergent adverse events (AEs) and clinical laboratory evaluations. After 26 weeks of mipomersen administration, LDL-c was reduced by 47 ± 18% (P < 0.001 vs. placebo). apoB and Lp(a) were also significantly reduced by 46 and 27%, respectively (P < 0.001 vs. placebo). Four mipomersen (19%) and two placebo subjects (17%) discontinued dosing prematurely due to AEs. Persistent liver transaminase increases ≥ 3× the upper limit of normal were observed in seven (33%) subjects assigned to mipomersen. In selected subjects, liver fat content was assessed, during and after treatment, using magnetic resonance spectroscopy. Liver fat content in these patients ranged from 0.8 to 47.3%. Liver needle biopsy was performed in two of these subjects, confirming hepatic steatosis with minimal inflammation or fibrosis.
The present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD. The long-term follow-up of liver safety is required.
ClinicalTrials.gov identifier: NCT00707746.
一项随机、双盲、安慰剂对照的研究旨在评估米泊美生（一种载脂蛋白 B-100 [apoB] 合成抑制剂）在他汀类药物不耐受且心血管疾病 [CVD] 风险较高的患者中的安全性和疗效。
33 名因他汀类药物不耐受而未接受他汀类药物治疗的患者，每周接受 200mg 米泊美生或安慰剂（2:1 随机分组）皮下注射治疗 26 周。主要终点是从基线到第 28 周时 LDL 胆固醇（LDL-c）的百分比变化。其他疗效终点为 apoB 和脂蛋白 a [Lp(a)] 的百分比变化。安全性通过治疗后出现的不良事件（AE）和临床实验室评估的发生率来确定。米泊美生治疗 26 周后，LDL-c 降低了 47±18%（P<0.001 与安慰剂相比）。apoB 和 Lp(a) 也分别显著降低了 46%和 27%（P<0.001 与安慰剂相比）。有 4 名（19%）米泊美生和 2 名（17%）安慰剂患者因 AE 提前终止治疗。有 7 名（33%）接受米泊美生治疗的患者出现持续的肝转氨酶升高≥3 倍正常上限。在接受和治疗后，对部分患者使用磁共振波谱法评估肝内脂肪含量。这些患者的肝内脂肪含量范围为 0.8-47.3%。对其中 2 名患者进行了肝活检，证实了伴有轻微炎症或纤维化的肝脂肪变性。
目前的数据表明，米泊美生可能是 CVD 风险较高的他汀类药物不耐受患者的潜在治疗选择。需要进行长期的肝安全性随访。
ClinicalTrials.gov 标识符：NCT00707746。
