Simvastatin compared to fluvastatin in the reduction of serum lipids and apolipoproteins in patients with ischaemic heart disease and moderate hypercholesterolaemia.

OBJECTIVE: Inhibitors of HMG-CoA reductase are widely used for the treatment of hypercholesterolaemia and have recently been shown in the Scandinavian Simvastatin Survival Study (4S), to reduce coronary mortality as well as total mortality in CH D patients. Although a couple of studies have already established the efficacy ratio between simvastatin and fluvastatin, one of the newest members of this class, we considered it to be important to verify the comparative efficacy in patients with coronary artery disease in the same type of patients that were included in 4S particularly since the previous studies include rather few patients with CHD, 17-28% only. METHODS AND RESULTS: Three Scandinavian lipid clinics participated in this randomized double-blind study and enrolled a total of 113 hypercholesterolaemic patients with a profile similar to the 4S patients, i.e. either a history of typical angina pectoris lasting at least three months or a myocardial infarction at least six months before the study and with moderate hypercholesterolaemia, total serum cholesterol between 5.5 and 8.0 mmol/l. After a diet run-in period lasting at least 8 weeks, followed by a two week placebo period, patients received treatment with active drug for a 16 week period, with measurement of lipids using the same technique and laboratory as was used in 4S. Patients were randomly assigned to simvastatin 20 mg or fluvastatin 20 mg. If after 6 weeks of double-blind treatment, the 4S total cholesterol target of < or = 5.2 mmol/l total serum cholesterol had not been reached, the dose was doubled at the next visit, i.e. at week 10 based upon blinded titration information from the central lipid laboratory like in the 4S study. A final assessment of serum lipids and lipoproteins was made at week 16. The mean percent reductions in LDL-cholesterol from baseline were 37% and 40% in the simvastatin group compared to 19% and 26% in the fluvastatin group, at weeks 10 and 16, respectively (p < 0.001). In the simvastatin group 18 percent of the patients needed an increase in the dose to 40 mg compared to 63 percent in the fluvastatin group (p < 0.001). At the 20 mg dosage, simvastatin produced a lowering of LDL-cholesterol approximately twice that of fluvastatin 20 mg and resulted in 82% of patients achieving the cholesterol target levels as defined in the 4S study, compared to 19% for fluvastatin. All other recorded lipid variables showed differences which favoured simvastatin over fluvastatin at comparable doses including serum triglyceride reductions where serum triglycerides at week 6 were borderline significantly different between the two groups. Patient tolerability of the two drugs was similar. CONCLUSION: At the recommended doses in patient with angina or a prior MI and mild to moderate hypercholesterolaemia simvastatin is considerably more effective than fluvastatin in lowering serum total cholesterol, LDL-cholesterol as well as other serum lipid risk factors. At an average titrated dose of 32 mg less than 50% of the fluvastatin patients reached the 4S cholesterol target of < 5.2 mmol/l compared to 89% of the simvastatin patients at an average dose of 23 mg daily and only 13% of the fluvastatin patients achieved an LDL-cholesterol reduction of at least 40% compared to 63% of the simvastatin patients.