COMPARISON OF THE SHORT-TERM EFFICACY AND TOLERABILITY OF LOVASTATIN AND SIMVASTATIN IN THE MANAGEMENT OF PRIMARY HYPERCHOLESTEROLEMIA

OBJECTIVES: To compare the safety and efficacy of lovastatin and simva statin in patients with primary hypercholesterolemia. METHODS: Fourtee n Canadian centres participated in this double-blind, randomized, para llel-design study with a six-week screening period, a four-week placeb o baseline period and an 18-week active treatment period. Patients wer e included in the study if their total cholesterol (TC) was at least 6 .2 mmol/L and total triglycerides (TG) were 4.0 mmol/L or less at base line. Half of the patients were in stratum [(TC6.2 to 7.8 mmol/L at ba seline and placebo period) and half in stratum II (TC greater than 7.8 mmol/L). The initial dose of lovastatin or simvastatin (20 and 10 mg/ day, respectively) was doubled if the patient's cholesterol was greate r than 5.2 mmol/L after six and/or 12 weeks, to a maximum of 80 mg/day lovastatin or 40 mg/day simvastatin. Of 298 randomized patients, two had baseline data only (and were excluded from the efficacy analysis), while 77 were treated with lovastatin and 74 with simvastatin in stra tum 1, and 72 were on lovastatin and 75 on simvastatin in stratum II. RESULTS: In stratum 1, both lovastatin and simvastatin lowered TC (-26 .0% in both the lovastatin and simvastatin groups), low density lipopr otein (LDL) cholesterol (-33.4% in lovastatin and -34.4% in simvastati n), TG (-11.4% in lovastatin and -16.2% in simvastatin), apolipoprotei n (apo)-B (-24.8% in lovastatin and -26.3% in simvastatin) and the TC: high density lipoprotein (HDL) cholesterol ratio (from 6.65 to 4.73 in lovastatin and from 6.45 to 4.46 in simvastatin), and increased HDL c holesterol (+3.6% in lovastatin and +7.8% in simvastatin) and apo-Al ( +6.3% in lovastatin and +9.0% in simvastatin) with P<0.001 in all with in-group tests except for HDL cholesterol (P<0.05). Similar results we re obtained in stratum 11 for TC (-30.7% in lovastatin and -30.3% in s imvastatin), LDL cholesterol (-37.6% in lovastatin and -36.8% in simva statin), TG (-21.9% in lovastatin and -16.9% in simvastatin), apo-B (- 32.0% in lovastatin and -31.7% in simvastatin), TC:HDL cholesterol rat io (from 8.62 to 5.47 in lovastatin and from 8.96 to 5.77 in simvastat in), HDL cholesterol (+9.7% in lovastatin and +7.5% in simvastatin) an d apo-Al (+7.2% in lovastatin and +8.8% in simvastatin), with P<0.001 in all within-group tests. Serious adverse events (clinical and labora tory) were reported in four patients in the lovastatin group and three in die simvastatin group. The most reported nonserious adverse effect s were gastrointestinal tract (15 patients in the lovastatin group and 16 in the simvastatin group) and musculskeletal (14 patients in the l ovastatin group and 11 in the simvastatin group). Medication was withd rawn in eight patients. CONCLUSIONS: Both lovastatin and simvastatin w ere found to be effective and well tolerated in each stratum. However, there were no significant differences between lovastatin and simvasta tin in the treatment of moderate or severe primary hypercholesterolemi a.