Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years.

Aims: This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE).

Methods: Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3-5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months.

Results: The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of > or = 3-fold consecutive elevations of liver transaminases (0.7%) or > or = 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of approximately 18% were maintained throughout the study.

Conclusions: Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction.