Background: The combination tablet containing ezetimibe and simvastatin (EZE/SIMVA), inhibits both the intestinal absorption and endogenous production of cholesterol, providing significantly greater low-density lipoprotein cholesterol (LDL-C) lowering than EZE or SIMVA alone. The purpose of this pooled analysis was to evaluate the consistency of efficacy (i.e., between-treatment difference) of EZE/SIMVA versus SIMVA within several selected subgroups of patients with primary hypercholesterolemia.
Methods: For the present analysis, data were pooled from three similarly designed, 12-week, randomized, double-blind, placebo-controlled factorial studies consisting of 3083 patients with primary hypercholesterolemia (n = 311 in placebo group; n = 302 in EZE group; n = 1234 in pooled SIMVA group; n = 1236 in pooled EZE/SIMVA group). In these clinical studies, primary hypercholesterolemia was defined as an LDL-C value between 145 and 250 mg/dL inclusive and a triglyceride (TG) level of less than 350 mg/dL. The results for the pooled SIMVA and pooled EZE/SIMVA groups were used for the present analyses. The pooled analyses focused on the consistency of the between-treatment differences (i.e., incremental effect) for EZE/SIMVA (pooled across doses) versus SIMVA (pooled across doses) on various lipid and non-lipid parameters within different patient subgroups defined according to gender, race (Caucasian, Non-Caucasian), baseline age (< 65, > or = 65 years), baseline LDL-C (< 160, > or = 160 mg/dL), and coronary heart disease (CHD) history. Tolerability was also examined for pooled EZE/SIMVA and pooled SIMVA within these selected subgroups. In a modified intention-to-treat analysis, an ANOVA model was used for testing the consistency of pooled treatment effects on lipid and non-lipid parameters within each selected subgroup.
Results: For the entire cohort, baseline lipid profiles were similar for the patients in the pooled EZE/SIMVA group compared with those in the pooled SIMVA group. Treatment with EZE/SIMVA led to significant (p < 0.001) incremental improvements in LDL-C, non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, TG and high sensitivity C-reactive protein compared to SIMVA, across the entire cohort. These changes were consistent within each of the selected subgroups. Moreover, more patients attained LDL-C goal levels < 100 mg/dL with EZE/SIMVA than with SIMVA in the entire cohort and this was consistent across all subgroups, except baseline LDL-C. In this pooled retrospective analysis, treatment with EZE/SIMVA was generally well tolerated across subgroups, with a safety profile similar to SIMVA monotherapy. Although this pooled analysis was performed on a large cohort of patients with primary hypercholesterolemia, the results of this analysis were specific for this select patient population and generalizations to other populations should be applied with caution.
Conclusion: The enhanced lipid-altering effects of EZE/SIMVA versus those of SIMVA observed in the entire cohort were consistent within all subgroups examined. EZE/SIMVA represents an effective and well-tolerated therapeutic option for the treatment of a wide range of patient subgroups with primary hypercholesterolemia.