与其他强化降脂策略相比，从他汀类单药治疗转换为依折麦布/辛伐他汀联合治疗对有症状心血管疾病的糖尿病患者脂蛋白亚类的影响。

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid-Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease.

作者信息

Le Ngoc-Anh, Tomassini Joanne E, Tershakovec Andrew M, Neff David R, Wilson Peter W F

机构信息

Biomarker Core Laboratory, Atlanta VAMC, Decatur, GA (N.A.L., P.F.W.).

Merck Research Laboratories, Kenilworth, NJ (J.E.T., A.M.T., D.R.N.).

出版信息

J Am Heart Assoc. 2015 Oct 20;4(10):e001675. doi: 10.1161/JAHA.114.001675.

BACKGROUND

Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL-C-lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL-C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose-doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low- and high-density lipoprotein particle number and lipoprotein-associated phospholipase A2 [Lp-PLA2]) was assessed.

METHODS AND RESULTS

Treatment effects on low- and high-density lipoprotein particle number (by NMR) and Lp-PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low-density lipoprotein-particle number numerically more than did statin dose-doubling and was comparable with R10 (-133.3, -94.4, and -56.3 nmol/L, respectively; P>0.05). Increases in high-density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose-doubling (1.5 and -0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low-density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose-doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp-PLA2 activity significantly more than did statin dose-doubling (-28.0 versus -3.8 nmol/min per mL, P<0.05) and was comparable with R10 (-28.0 versus -18.6 nmol/min per mL; P>0.05); effects on Lp-PLA2 concentration were modest.

CONCLUSIONS

In diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp-PLA2 activity more than did statin dose-doubling and was comparable with R10, consistent with its lipid effects.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

背景

糖尿病和心血管疾病患者单纯使用他汀类药物治疗可能无法充分降低低密度脂蛋白胆固醇（LDL-C）水平，部分原因是致动脉粥样硬化性血脂异常。对于这些患者可考虑采用更强化的LDL-C降低治疗。一项既往随机对照研究表明，有症状心血管疾病的糖尿病患者从辛伐他汀20mg（S20）或阿托伐他汀10mg（A10）转换为依折麦布/辛伐他汀10/20mg（ES10/20）联合治疗，与他汀类药物剂量加倍（至S40或A20）或换用瑞舒伐他汀10mg（R10）相比，LDL-C降低幅度更大。评估了这些治疗方案对致动脉粥样硬化性血脂异常新生物标志物（低密度和高密度脂蛋白颗粒数量以及脂蛋白相关磷脂酶A2 [Lp-PLA2]）的影响。

方法与结果

使用研究中358名受试者的血浆样本评估对低密度和高密度脂蛋白颗粒数量（通过核磁共振）以及Lp-PLA2（通过酶联免疫吸附测定）的治疗效果。转换至ES10/20在数值上比他汀类药物剂量加倍更多地降低了低密度脂蛋白颗粒数量，且与R10相当（分别为-133.3、-94.4和-56.3nmol/L；P>0.05）。与他汀类药物剂量加倍相比，转换至ES10/20后高密度脂蛋白颗粒数量的增加显著更大（分别为1.5和-0.5μmol/L；P<0.05），且与R10相当（0.7μmol/L；P>0.05）。达到低密度脂蛋白颗粒数量水平<990nmol/L的患者百分比，ES10/20组为62.4%，他汀类药物剂量加倍组为54.1%，R10组为57.0%。转换至ES10/20比他汀类药物剂量加倍更显著地降低了Lp-PLA2活性（分别为-28.0和-3.8nmol/分钟每毫升，P<0.05），且与R10相当（分别为-28.0和-18.6nmol/分钟每毫升；P>0.05）；对Lp-PLA2浓度的影响较小。