SEQUENTIAL MANAGEMENT OF HYPERCHOLESTEROLEMIA WITH A FIBRATE AND SIMVASTATIN - THE BELGIAN GENERAL-PRACTITIONERS TRIAL

This 24-week prospective, open-label study, conducted by 1198 general practitioners, evaluated the efficacy and safety of sequential fibrate and simvastatin therapy in 6745 patients (mean +/- SD; 60 +/- 11 year s; 37% male) with severe hypercholesterolaemia [total cholesterol (TC) >290 mg/dl]. The study design closely matched the 1991 Belgian health care regulations that imposed fibrates as first-line drugs in diet-res istant dyslipidaemic subjects and restricted the use of a statin to pa tients not sufficiently controlled by diet and a fibrate. Lipid values at baseline after a 12-week diet run-in period, that resulted in a me an 3.8% TC decrease, were TC 329 +/- 37 mg/dl, low-density lipoprotein cholesterol (LDL-C) 236 +/- 39 mg/dl, high-density lipoprotein choles terol (HDL-C) 55 +/- 18 mg/dl and triglycerides (TG) 187 +/- 79 mg/dl. Mean percentage changes in 6422 patients who completed the 12-week fi brate treatment (bezafibrate n = 792; ciprofibrate n = 2312; fenofibra te n = 2770; gemfibrozil n = 548) were -14%, -17%, +8% and -16% for TC , LDL-C, HDL-C and TG, respectively. Target goals [TC <300 mg/dl in su bjects at moderate risk for coronary heart disease (CHD); TC <250 mg/d l or LDL-C <160 mg/dl in high CHD risk subjects] were reached in 45% o f patients. Subsequently, 3311 subjects who had failed to achieve targ et goals with diet and a fibrate were enrolled in the diet plus simvas tatin therapy phase (weeks 12 to 24). Median simvastatin dosages were 10 and 20mg daily at weeks 18 and 24, respectively. Mean percentage ch anges from baseline at weeks 18 and 24 were -23 and -29% for TC, -30 a nd -38% for LDL-C, +11 and +12% for HDL-C, and -11 and -13% for TG. St udy protocol target goals were reached by 69 and 84% of patients at we eks 18 and 24, respectively. LDL-C target goals set by the 1993 Nation al Cholesterol Education Program II guidelines were met by 13% of pati ents with fibrate (week 12) and, in those not sufficiently controlled with fibrate, by 19% receiving simvastatin 10mg daily (week 18) and by 34% on simvastatin 20mg daily (week 24). The study drugs were general ly well tolerated. Drug-related adverse events occurred in 3.5% of pat ients on fibrate and in 6.5% on simvastatin. Single transaminase eleva tions greater than 3 times the upper limit of normal were observed in 0.4 and 0.7% of patients on fibrate and simvastatin, respectively. Myo pathy was not observed. In conclusion, this study of 6745 severely hyp ercholesterolaemic patients demonstrated a low efficacy of dietary cou nselling in a primary care setting, a mean 17% LDL-C lowering by fibra te therapy, and a mean 38% LDL-C decrease from baseline with simvastat in 20mg daily in patients not sufficiently controlled by fibrate. Fibr ates and simvastatin had a comparable safety profile.