Summary
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 hypercholesterolemia (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 and 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 (fluvastatimsimvastatin). Both drugs were well tolerated, with no significant difference in the incidence of drug-related adverse events.
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References
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease; the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9
Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–7
Livine GN, Keaney JF, Vita JA. Cholesterol reduction in cardiovascular disease. N Engl J Med 1995; 322: 512–21
Holme I. Cholesterol reduction and its impact on coronary artery disease and total mortality. Am J Cardiol 1995; 76: 10C–17C
Illingworth DR, Erkelens DW, Keller U, et al. Defined daily doses in relation to hypolipidaemic efficacy of lovastatin, pravastatin and simvastatin. Lancet 1994; 343: 1554–5
Mitchel YB. The long-term tolerability profile of lovastatin and simvastatin. Atherosclerosis 1992; 97: S33–S39
Jacotot B, Benghozi R, Pfister P, et al. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolemia. Am J Cardiol 1995; 76: 54A–56A
Haasis R, Berger J. Fluvastatin versus Lovastatin — eine randomisierte, doppelblinde, multizentrische Parallelgrup-penstudie zur Effektivität und Sicherheit einer Lipidsenkung. Herz Kreisl 1995; 27: 375–80
Haasis R, Berger J, Andersson F, et al. A pharmacoeconomic evaluation of fluvastatin and lovastatin in primary hyperchol-esterolaemia. Br J Med Econ 1996; 10: 145–57
Ose L, Scott R and the Simvastatin-Fluvastatin Study Group. Double-blind comparison of the efficacy and tolerability of simvastatin and fluvastatin in patients with primary hyper-cholesterolaemia. Clin Drug Invest 1995; 10: 127–38
Illingworth DR, Stein EA, Knopp RH, et al. A randomized multicenter trial comparing the efficacy of simvastatin and fluvastatin. J Cardiovasc Pharmacol Ther 1996; 1: 23–30
Deslypere JP. Simvastatin-fluvastatin comparative study [correspondence]. Clin Drug Invest 1996; 11: 362–3
Deslypere JP. Simvastatin-fluvastatin comparative study — continued [correspondence]. Clin Drug Invest 1996; 12: 57
Ose L. Simvastatin-fluvastatin comparative study — continued [correspondence]. Clin Drug Invest 1996; 11: 363–4
Ose L. Simvastatin-fluvastatin comparative study — continued [correspondence]. Clin Drug Invest 1996; 12: 57
Friedewald T, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972; 6: 499–502
European Atherosclerosis Society. Prevention of coronary heart disease — scientific background and new clinical guidelines. Nutr Metab Cardiovasc Dis 1992; 2: 113–56
Kjekshus J, Pedersen TR. Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1995; 76: 64C–68C
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Schulte, KL., Beil, S. Efficacy and Tolerability of Fluvastatin and Simvastatin in Hypercholesterolaemic Patients. Clin. Drug Invest. 12, 119–126 (1996). https://doi.org/10.2165/00044011-199612030-00001
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DOI: https://doi.org/10.2165/00044011-199612030-00001