Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

@article{citeulike:2618823, abstract = {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 intimamedia thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intimamedia thickness, which was defined as the average of the means of the far-wall intimamedia 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 intimamedia thickness, was 0.0058{+/-}0.0037 mm in the simvastatin-only group and 0.0111{+/-}0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intimamedia 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 intimamedia thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 .) 10.1056/NEJMoa0800742}, author = {Kastelein, John J. and Akdim, Fatima and Stroes, Erik S. and Zwinderman, Aeilko H. and Bots, Michiel L. and Stalenhoef, Anton F. and Visseren, Frank L. and Sijbrands, Eric J. and Trip, Mieke D. and Stein, Evan A. and Gaudet, Daniel and Duivenvoorden, Raphael and Veltri, Enrico P. and Marais, David A. and de Groot, Eric and Investigators, The E. }, citeulike-article-id = {2618823}, doi = {10.1056/NEJMoa0800742}, journal = {N Engl J Med}, keywords = {hplp, rct, risk, vasculardisease}, month = {March}, pages = {NEJMoa0800742+}, posted-at = {2008-04-07 15:49:31}, priority = {2}, title = {Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia}, url = {http://dx.doi.org/10.1056/NEJMoa0800742}, year = {2008} }

TY - JOUR ID - citeulike:2618823 L3 - citeulike-article-id:2618823 TI - Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia JF - N Engl J Med SP - NEJMoa0800742 N2 - 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 intimamedia thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intimamedia thickness, which was defined as the average of the means of the far-wall intimamedia 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 intimamedia thickness, was 0.0058{+/-}0.0037 mm in the simvastatin-only group and 0.0111{+/-}0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intimamedia 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 intimamedia thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 .) 10.1056/NEJMoa0800742 KW - hplp KW - rct KW - risk KW - vasculardisease AU - Kastelein, John AU - Akdim, Fatima AU - Stroes, Erik AU - Zwinderman, Aeilko AU - Bots, Michiel AU - Stalenhoef, Anton AU - Visseren, Frank AU - Sijbrands, Eric AU - Trip, Mieke AU - Stein, Evan AU - Gaudet, Daniel AU - Duivenvoorden, Raphael AU - Veltri, Enrico AU - Marais, David AU - de Groot, Eric AU - Investigators, The PY - 2008/03/30/ UR - http://dx.doi.org/10.1056/NEJMoa0800742 ER -