Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia
摘要：该研究主要验证了依折麦布对延缓动脉粥样硬化进程的疗效。对有家族性高胆固醇血症的患者，采用依折麦布和辛伐他汀治疗后，内膜和中膜没有出现厚度的变化，但是相比于单一的辛伐他汀，LDL-C和CRP明显下降。
Background Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown.
Methods We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima–media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the
mean carotid-artery intima–media thickness, which was defined as the average of the means of the far-wall intima–media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries.
Results The primary outcome, the mean (±SE) change in the carotid-artery intima–media thickness, was 0.0058±0.0037 mm in the simvastatin-only group and 0.0111±0.0038mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P = 0.29). Secondary outcomes (consisting of other variables regarding the intima–media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (±SD) LDL cholesterol level was 192.7±60.3 mg per deciliter(4.98±1.56 mmol per liter) in the simvastatin group and 141.3±52.6 mg per deciliter(3.65±1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups.
Conclusions In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima–media thickness,as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein.
