Cerivastatin in primary hyperlipidemia--a multicenter analysis of efficacy and safety

Cerivastatin, a novel, synthetic, and enantiomerically pure 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been administered, in clinical trials, to over 2700 patients with primary hypercholesterolemia, of whom over 1000 received treatment for periods of up to 1 year. A global, pooled analysis of the efficacy, safety, and tolerability of cerivastatin was performed on data obtained from all randomized, double-blind studies in which cerivastatin at doses of 0.025-0.4 mg/day were compared with either placebo or active comparators. All studies had a 10-week, diet-controlled run-in period, the last 6 weeks of which included administration of single-blind placebo. Efficacy analysis of the pooled data at 8 weeks post-randomization showed that in comparison with placebo, cerivastatin achieved significant dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C), the primary efficacy parameter, of between 14.2 and 36.1%. Reductions in LDL-C were accompanied by significant reductions in total cholesterol and triglycerides, together with increases in high-density lipoprotein cholesterol (HDL-C). The magnitude of the reduction in plasma triglycerides was strongly related to baseline triglyceride levels. In patients with baseline plasma triglycerides of >250 mg/dl, treatment with 0.4 mg/day cerivastatin decreased these levels by 37%. Cerivastatin was well tolerated, with the type and incidence of clinical adverse effects comparable to that of placebo and comparator drugs. The incidence of biochemical adverse effects was also similar to that seen with either placebo or comparator drugs and was independent of the dose of cerivastatin. Less than 1% of patients treated with cerivastatin at doses of 0.025-0.4 mg/day experienced clinically significant increases in either hepatic transaminases (> 3 x the upper limit of normal) or creatine phosphokinase (CPK) (> 5 x the upper limit of normal). The good tolerability of cerivastatin was reflected in a low rate of premature withdrawal from treatment, below or comparable to that of placebo-treatment. The pooled efficacy and safety analyses have shown that at 1% of the doses of other statins, cerivastatin is a safe, well-tolerated, and highly effective HMG-CoA reductase inhibitor for the treatment of type IIa and IIb hypercholesterolemia.