Combination therapy with ezetimibe and simvastatin for 6 weeks provides greater reductions in low-density lipoprotein cholesterol (LDL-C) compared with rosuvastatin at the usual starting, next highest, and maximum doses of each drug, according to a randomized, double-blind, parallel-group, multicenter trial published in the journal Current Medical Research and Opinion.
In the trial, 2,855 participants from 214 US sites who had LDL-C levels ≥145 mg/dL but <250 mg/dL and triglyceride levels ≤350 mg/dL were randomly assigned to receive either once-daily, 1-tablet ezetimibe plus simvastatin at doses of 10/20 mg (usual starting dose) (n=492), 10/40 mg (next highest dose) (n=493), or 10/80 mg (maximum dose) (n=493), or once-daily rosuvastatin monotherapy at doses of 10 mg (usual starting dose) (n=492), 20 mg (next highest dose) (n=495), or 40 mg (maximum dose) (n=494). Patient randomization was stratified by LDL-C level (<160 mg/dL, ≥160 mg/dL, or ≥190 mg/dL) to ensure balance between the 2 treatment groups. After a 4-week placebo and diet run-in period and 6 weeks of active drug therapy, researchers assessed study end points including the percent change from baseline in LDL-C and other pertinent cholesterol measurements, the percentage of patients achieving national LDL-C treatment goals, the percentage of patients and high-risk patients who attained LDL-C levels <70 mg/dL, and numerous safety variables.
At the end of active drug therapy, significantly more patients receiving the usual starting, next highest, and maximum doses of ezetimibe plus simvastatin experienced reduced LDL-C levels than those receiving the corresponding usual starting, next highest, and maximum doses of rosuvastatin monotherapy (percent difference between treatments range, 2.5%–5.7%; P≤.001 for all comparisons). As a result of these LDL-C reductions, a greater proportion of patients receiving ezetimibe plus simvastatin attained national LDL-C treatment goals compared with patients receiving rosuvastatin monotherapy (95.9% vs 93.0%; P≤.001). Additionally, a greater proportion of both total study participants and high-risk study participants attained LDL-C levels <70 mg/dL following ezetimibe plus simvastatin therapy compared with rosuvastatin therapy at the usual starting, next highest, and maximum doses and across doses (P≤.005 for all comparisons).
Both treatments were generally well tolerated. However, there was a trend toward participants receiving ezetimibe plus simvastatin having liver enzyme abnormalities more frequently than those receiving rosuvastatin (P=.09). Also, a significantly higher percentage of patients with proteinuria was observed in the rosuvastatin group compared with the ezetimibe plus simvastatin group (P<.001).
The authors said that national and international guidelines reflect the importance of lowering patients' LDL-C levels to reduce CHD risk and that "a log-linear relationship exists between LDL cholesterol levels and CHD risk, such that a 1% reduction in LDL cholesterol is predicted to reduce the risk of CHD by approximately 1%." However, despite the well-known relationship between LDL-C and CHD risk, patients often fail to attain treatment LDL-C goals, thus making it necessary for researchers to develop therapies that can achieve very low LDL-C levels.
In commenting on the importance of the study, the authors remarked that "the results of this study provide clinicians with information regarding the use of these drugs in comparable clinical situations (ie, for initial therapy and for subsequent use at higher doses as well)."
Although the average levels of LDL-C observed in patients receiving ezetimibe/simvastatin combination therapy were similar to those in clinical trials, such as the Treating New Targets (TNT) study, "it should be noted that the effect of ezetimibe/simvastatin or rosuvastatin upon the reduction of coronary events in clinical trials has not yet been assessed," the authors stated.
SOURCE Catapano AL, Davidson MH, Ballantyne CM, et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin. 2006;22:2041–2051.