International multicentre comparison of cerivastatin with placebo and simvastatin for the treatment of patients with primary hypercholesterolaemia. International Cerivastatin Study Group

Abstract

An international multicentre double-blind randomised trial compared the efficacy and safety of cerivastatin (0.025, 0.05, 0.1 and 0.2 mg once daily) with placebo and simvastatin (20 mg) over a period of 12 weeks, with study extensions to 52 and 100 weeks. The primary efficacy parameter was the percentage change in low density lipoprotein cholesterol (LDL-C). This was reduced from the baseline by 12.5% (0.025 mg) to 30.6% (0.2 mg) compared with falls of 2.0% on placebo and 40.3% on simvastatin. All four cerivastatin doses and simvastatin (20 mg) produced significantly greater falls than placebo (p < 0.0001) and the decrease in LDL-C was dose-dependent for cerivastatin. Simvastatin produced significantly greater falls than any cerivastatin dose or placebo (p < 0.0001). The effect was maintained at 1 year but somewhat attenuated at 100 weeks. Significant falls were also seen in serum total cholesterol and triglycerides. High density lipoprotein cholesterol (HDL-C) levels were significantly increased by cerivastatin (0.1 and 0.2 mg) and simvastatin (20 mg) at 12 weeks and increased further by 100 weeks. Mean fasting apolipoprotein A1 and lipoprotein A1 were increased and apolipoprotein B decreased by cerivastatin and simvastatin therapy. All doses of cerivastatin produced significant falls in the total cholesterol/HDL-C ratio at 12 weeks (0.5-1.6) compared with a fall of 2.1 for simvastatin (20 mg). Cerivastatin was well tolerated. Elevations in creatine phosphokinase, aspartate aminotransferase and alanine aminotransferase were mostly minor and transitory. Vital signs, electrocardiogram determinations, urinalysis and ophthalmic assessment showed similar results for both drugs. Cerivastatin, at doses of 0.1 mg and 0.2 mg daily, is considered to be of therapeutic value in the treatment of patients with primary hypercholesterolaemia, with 0.2 mg cerivastatin achieving reductions of LDL-C and total cholesterol similar to those achieved in the WOSCOP and CARE studies.