ODYSSEY FH I和FH II：735例杂合子家族性高胆固醇血症患者接受阿利西尤单抗治疗78周的结果
ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.
作者信息
Kastelein John J P, Ginsberg Henry N, Langslet Gisle, Hovingh G Kees, Ceska Richard, Dufour Robert, Blom Dirk, Civeira Fernando, Krempf Michel, Lorenzato Christelle, Zhao Jian, Pordy Robert, Baccara-Dinet Marie T, Gipe Daniel A, Geiger Mary Jane, Farnier Michel
机构信息
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room F4-159.2, 1105 AZ Amsterdam, The Netherlands
Columbia University, New York, NY, USA.
出版信息
Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.
AIMS
To assess long-term (78 weeks) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia (HeFH) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy (LLT).
METHODS AND RESULTS
In two randomized, double-blind studies (ODYSSEY FH I, n = 486; FH II, n = 249), patients were randomized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks (Q2W). Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L (70 mg/dL). Primary endpoint (both studies) was percentage change in calculated LDL-C from baseline to Week 24. Mean LDL-C levels decreased from 3.7 mmol/L (144.7 mg/dL) at baseline to 1.8 mmol/L (71.3 mg/dL; -57.9% vs. placebo) at Week 24 in patients randomized to alirocumab in FH I and from 3.5 mmol/L (134.6 mg/dL) to 1.8 mmol/L (67.7 mg/dL; -51.4% vs. placebo) in FH II (P < 0.0001). These reductions were maintained through Week 78. LDL-C <1.8 mmol/L (regardless of cardiovascular risk) was achieved at Week 24 by 59.8 and 68.2% of alirocumab-treated patients in FH I and FH II, respectively. Adverse events resulted in discontinuation in 3.4% of alirocumab-treated patients in FH I (vs. 6.1% placebo) and 3.6% (vs. 1.2%) in FH II. Rate of injection site reactions in alirocumab-treated patients was 12.4% in FH I and 11.4% in FH II (vs. 11.0 and 7.4% with placebo).
CONCLUSION
In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT, alirocumab treatment resulted in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated.
CLINICAL TRIAL REGISTRATION
Cinicaltrials.gov (identifiers: NCT01623115; NCT01709500).
目的
评估在杂合子家族性高胆固醇血症（HeFH）患者中，在最大耐受降脂治疗（LLT）下低密度脂蛋白胆固醇（LDL-C）控制不佳时，阿利西尤单抗的长期（78周）治疗效果。
方法与结果
在两项随机、双盲研究（ODYSSEY FH I，n = 486；FH II，n = 249）中，患者按2:1随机分组，每2周接受75 mg阿利西尤单抗或安慰剂治疗（Q2W）。如果第8周时LDL-C≥1.8 mmol/L（70 mg/dL），则在第12周将阿利西尤单抗剂量增加至150 mg Q2W。主要终点（两项研究）是从基线到第24周计算的LDL-C的百分比变化。在FH I中，随机接受阿利西尤单抗治疗的患者，其平均LDL-C水平从基线时的3.7 mmol/L（144.7 mg/dL）降至第24周时的1.8 mmol/L（71.3 mg/dL；与安慰剂相比降低了57.9%）；在FH II中，从3.5 mmol/L（134.6 mg/dL）降至1.8 mmol/L（67.7 mg/dL；与安慰剂相比降低了51.4%）（P < 0.0001）。这些降低在第78周时仍得以维持。在FH I和FH II中，分别有59.8%和68.2%接受阿利西尤单抗治疗的患者在第24周时实现了LDL-C <1.8 mmol/L（无论心血管风险如何）。不良事件导致FH I中3.
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