EFFICACY AND TOLERABILITY OF FLUVASTATIN AND SIMVASTATIN IN HYPERCHOLESTEROLEMIC PATIENTS - A DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP COMPARISON

The efficacy and tolerability of simvastatin and fluvastatin were comp ared in a randomised, parallel-group study using marketed formulations of the drugs and identical encapsulation to ensure blindness. 120 pat ients with primary hypercholesterolaemia (LDL > 185 mg/dl), who entere d a run-in, washout period of 4 weeks (3 months in the case of previou s statin treatment), were randomised to fluvastatin 40mg or simvastati n 20mg once daily in the evening. After 4 weeks, the doses were double d (80 and 40mg once daily in the evening, respectively) in all patient s for another 6 weeks. There were no significant differences between t he 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 simvastati n were 24 and 34%. The difference between the treatment groups in tota l cholesterol and triglycerides, HDL-C and LDL-C, were not significant . At the end of the study, there was a positive correlation between ba seline 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 lowe st (< 200 mg/dl) to the middle two (200 to 237 mg/dl) and to the highe st (> 237 mg/dl) quartile of baseline LDL-C, fluvastatin reduced LDL-C by 16, 31 and 43%, respectively. The corresponding figures for simvas tatin were 37, 33 and 35%. Adverse events occurred in 18 patients on f luvastatin and in 28 patients on simvastatin treatment. In the simvast atin group, a causal relationship between adverse event and study drug was regarded as likely in 4 cases, but in no case for patients receiv ing fluvastatin. There were statistically, but not clinically, relevan t 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. T he mean CK levels increased during simvastatin and fluvastatin treatme nts by about 35 and 18%, respectively. Fluvastatin and simvastatin ind uced indistinguishable reductions in LDL-C on their highest and next-h ighest recommended doses. The potency ratio was 1:2 (fluvastatin:simva statin). Both drugs were well tolerated, with no significant differenc e in the incidence of drug-related adverse events.