Efficacy and tolerability of fluvastatin and simvastatin in hypercholesterolaemic patients - A double-blind, randomised, parallel-group comparison

The efficacy and tolerability of simvastatin and fluvastatin were compared in a randomised, parallel-group study using marketed formulations of the drugs and identical encapsulation to ensure blindness. 120 patients with primary hypercholesterolaemia (LDL > 185 mg/dl), who entered a run-in, washout period of 4 weeks (3 months in the case of previous statin treatment), were randomised to fluvastatin 40mg or simvastatin 20mg once daily in the evening. After 4 weeks, the doses were doubled (80 and 40mg once daily in the evening, respectively) in all patients for another 6 weeks. There were no significant differences between the 2 groups at randomisation. Mean LDL-C fell by 24% by the end of the first 4 weeks on fluvastatin 40mg once daily and by 31% after another 6 weeks on 80mg once daily. The corresponding decreases on simvastatin were 24 and 34%. The difference between the treatment groups in total cholesterol and triglycerides, HDL-C and LDL-C, were not significant. At the end of the study, there was a positive correlation between baseline LDL-C and percentage LDL-C reduction in the fluvastatin group (p < 0.001) but not in the simvastatin group (p = 0.752). From the lowest (< 200 mg/dl) to the middle two (200 to 237 mg/dl) and to the highest (> 237 mg/dl) quartile of baseline LDL-C, fluvastatin reduced LDL-C by 16, 31 and 43%, respectively. The corresponding figures for simvastatin were 37, 33 and 35%. Adverse events occurred in 18 patients on fluvastatin and in 28 patients on simvastatin treatment. In the simvastatin group, a causal relationship between adverse event and study drug was regarded as likely in 4 cases, but in no case for patients receiving fluvastatin. There were statistically, but not clinically, relevant increases in aminotransferases (ASAT and ALAT) and creatine kinase (CK) in both groups. The mean increases in ASAT and ALAT were about 42 acid 55% on simvastatin and 34 and 27% on fluvastatin, respectively. The mean CK levels increased during simvastatin and fluvastatin treatments by about 35 and 18%, respectively. Fluvastatin and simvastatin induced indistinguishable reductions in LDL-C on their highest and next-highest recommended doses. The potency ratio was 1:2 (fluvastatin:simvastatin). Both drugs were well tolerated, with no significant difference in the incidence of drug-related adverse events.