A multi-centre, randomised, double-blind 14-week extension study examining the long-term safety and efficacy profile of the ezetimibe/simvastatin combination tablet.

The objective of this study was to compare the efficacy and safety profile of ezetimibe/simvastatin (EZE/SIMVA) tablet and SIMVA monotherapy. This was an extension study of a randomised, double-blind, placebo-controlled study in patients with primary hypercholesterolaemia. Protocol-compliant patients who completed the 12-week base study were eligible to enter a randomised, double-blind, 14-week extension study and were administered 1 of 8 daily treatments: EZE/SIMVA 10/10-, 10/20-, 10/40- or 10/80-mg, or SIMVA 10-, 20-, 40- or 80-mg. Patients receiving these treatments during the base study remained on the same treatment in the extension. Patients administered placebo or EZE 10-mg monotherapy during the base study were re-randomised to EZE/SIMVA 10/10 mg or SIMVA 80 mg. The primary analysis was mean per cent change in low-density lipoprotein cholesterol (LDL-C) from baseline to extension study end-point. Mean changes from baseline in LDL-C of -38.8% and -53.7% were observed for pooled SIMVA and pooled EZE/SIMVA respectively. The between treatment difference of -14.9% (95% confidence interval: -16.4, -13.3) was statistically significant (p < 0.001). The incremental LDL-C lowering effect of EZE/SIMVA compared with the corresponding dose of SIMVA alone was consistent across the dose range (p < 0.001 for each between-group comparison). More patients receiving EZE/SIMVA than SIMVA achieved LDL-C concentrations < 100 mg/dl and < 70 mg/dl (p < 0.001 for both goals). EZE/SIMVA was generally well tolerated with a safety profile similar to SIMVA monotherapy. There were no significant between-group differences in the incidences of clinically significant elevations in liver transaminase or creatine kinase levels. In conclusion, EZE/SIMVA had a comparable safety and tolerability profile and was more efficacious than SIMVA monotherapy for up to 6 months.