International multicentre comparison of cerivastatin with placebo and simvastatin for the treatment of patients with primary hypercholesterolaemia

An international multicentre double-blind randomised trial compared the eff icacy and safety of cerivastatin (0.025, 0.05, 0.1 and 0.2 mg once daily) w ith placebo and simvastatin (20 mg) over a period of 12 weeks, with study e xtensions to 52 and 100 weeks. The primary efficacy parameter was the perce ntage change in low density lipoprotein cholesterol (LDL-C). This was reduc ed from the baseline by 12.5% (0.025 mg) to 30.6% (0.2 mg) compared with fa lls of 2.0% on placebo and 40.3% on simvastatin. All four cerivastatin dose s 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 at tenuated at 100 weeks. Significant falls were also seen in serum total chol esterol and triglycerides. High density lipoprotein cholesterol (HDL-C) lev els were significantly increased by cerivastatin (0.1 and 0.2 mg) and simva statin (20 mg) at 12 weeks and increased further by 100 weeks. Mean fasting apolipoprotein Al and lipoprotein Al were increased and apolipoprotein B d ecreased by cerivastatin and simvastatin therapy. All doses of cerivastatin produced significant falls in the total cholesterol/HDL-C ratio at 12 week s (0.5-1.6) compared with a fall of 2.1 for simvastatin (20 mg). Cerivastat in was well tolerated. Elevations in creatine phosphokinase, aspartate amin otransferase and alanine aminotransferase were mostly minor and transitory. Vital signs, electrocardiogram determinations, urinalysis and ophthalmic a ssessment 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 tr eatment of patients with primary hypercholesterolaemia, with 0.2 mg cerivas tatin achieving reductions of LDL-C and total cholesterol similar to those achieved in the WOSCOP and CARE studies.