Jones Peter H, Davidson Michael H, Kashyap Moti L, Kelly Maureen T, Buttler Susan M, Setze Carolyn M, Sleep Darryl J, Stolzenbach James C
Baylor College of Medicine, Houston, TX 77030, USA.
Atherosclerosis. 2009 May;204(1):208-15. doi: 10.1016/j.atherosclerosis.2008.09.027. Epub 2008 Oct 5.
To evaluate a new formulation of fenofibric acid (ABT-335) co-administered with 2 doses of rosuvastatin in patients with mixed dyslipidemia.
In a phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 1445 patients with LDL-C>or=130 mg/dL, TG>or=150 mg/dL, and HDL-C<40 mg/dL (<50 mg/dL for women) were randomized to either ABT-335 (135 mg), rosuvastatin (10, 20, or 40 mg), or ABT-335+rosuvastatin 10 or 20 mg, and treated for 12 weeks. The primary efficacy comparisons were mean percent change in HDL-C and TG (ABT-335+rosuvastatin vs. corresponding dose of rosuvastatin), and LDL-C (ABT-335+rosuvastatin vs. ABT-335).
Combination therapy with ABT-335+rosuvastatin 10 mg resulted in significantly (p<0.001) greater improvements in HDL-C (20.3% vs. 8.5%) and TG (-47.1% vs. -24.4%) compared to rosuvastatin 10 mg; and LDL-C (-37.2% vs. -6.5%) compared to ABT-335. Similarly, significantly (p<0.001) greater improvements were observed with ABT-335+rosuvastatin 20 mg in HDL-C (19.0% vs. 10.3%) and TG (-42.9% vs. -25.6%) compared to rosuvastatin 20 mg; and LDL-C (-38.8% vs. -6.5%) compared to ABT-335 monotherapy. Greater improvements in multiple secondary endpoints were noted with combination therapy compared to prespecified monotherapies. Both combination therapy doses were generally well tolerated, with a safety profile consistent with ABT-335 and rosuvastatin monotherapies. No rhabdomyolysis or unexpected hepatic, renal, or muscle safety signals were identified.
In patients with mixed dyslipidemia, combination therapy with ABT-335+rosuvastatin resulted in more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies. This combination may be an appropriate therapeutic option to treat mixed dyslipidemia.
评估非诺贝特酸新制剂（ABT - 335）与两种剂量瑞舒伐他汀联合应用于混合性血脂异常患者的疗效。
在一项3期、多中心、随机、双盲、活性对照研究中，共有1445例低密度脂蛋白胆固醇（LDL - C）≥130mg/dL、甘油三酯（TG）≥150mg/dL且高密度脂蛋白胆固醇（HDL - C）<40mg/dL（女性<50mg/dL）的患者被随机分为ABT - 335（135mg）组、瑞舒伐他汀（10、20或40mg）组或ABT - 335 + 瑞舒伐他汀10或20mg组，并接受12周治疗。主要疗效比较为HDL - C和TG的平均变化百分比（ABT - 335 + 瑞舒伐他汀与相应剂量瑞舒伐他汀比较）以及LDL - C（ABT - 335 + 瑞舒伐他汀与ABT - 335比较）。
与10mg瑞舒伐他汀相比，ABT - 335 + 10mg瑞舒伐他汀联合治疗使HDL - C（20.3%对8.5%）和TG（-47.1%对-24.4%）有显著（p<0.001）更大幅度改善；与ABT - 335相比，LDL - C有显著改善（-37.2%对-6.5%）。同样，与20mg瑞舒伐他汀相比，ABT - 335 + 20mg瑞舒伐他汀使HDL - C（19.0%对10.3%）和TG（-42.9%对-25.6%）有显著（p<0.001）更大幅度改善；与ABT - 335单药治疗相比，LDL - C有显著改善（-38.8%对-6.5%）。与预先指定的单药治疗相比，联合治疗在多个次要终点有更大改善。两种联合治疗剂量总体耐受性良好，安全性与ABT - 335和瑞舒伐他汀单药治疗一致。未发现横纹肌溶解或意外的肝、肾或肌肉安全性信号。
在混合性血脂异常患者中，ABT - 335 + 瑞舒伐他汀联合治疗比单独使用任何一种单药治疗能更有效地控制多种血脂参数，安全性与两种单药治疗相似。这种联合治疗可能是治疗混合性血脂异常的合适治疗选择。
