COMBINED TREATMENT WITH PRAVASTATIN AND GEMFIBROZIL IN PATIENTS WITH REFRACTORY FAMILIAL COMBINED HYPERLIPEMIA - A CLINICAL-STUDY

This study was carried out to assess the efficacy and safety of combin ed therapy with pravastatin and gemfibrozil in patients with severe re fractory familial combined hyperlipidaemia. 26 patients (18 men and 8 women) with a mean age of 50 years (range 32 to 65 years) were include d in the study. Patients with secondary forms of dyslipoproteinaemia w ere excluded. All patients had been following a phase II American Hear t Association hypolipidaemic diet plus placebo for 1 month. Beginning at month 0, the patients received 4 months of combined treatment with a fixed dosage of gemfibrozil 1200 mg/day (divided into 2 equal doses) , and pravastatin 20 mg/day. The dosage of pravastatin was increased t o 40 mg/day after 1 month. At months-1, 0, 1, 2, 3 and 4 the following parameters were measured: total cholesterol (TC), low density lipopro tein cholesterol (LDL-C), very low density lipoprotein cholesterol (VL DL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG ), and apoproteins B and A-I. In the 17 patients free of coronary hear t disease (CHD) at baseline, the effect of treatment on the risk of my ocardial infarction (MI) was calculated. Before treatment initiation, the mean values (+/- SD) of the measured parameters were: TC = 309 +/- 23 mg/dl, TG = 253 +/- 35 mg/dl, LDL-C = 221 +/- 21 mg/dl, VLDL-C = 4 9 +/- 7 mg/dI, HDL-C = 34 +/- 5 mg/dl, apoprotein B = 170 +/- 10 mg/dl and apoprotein A-I = 118 +/- 11 mg/dl. After 4 months of combined tre atment the following percentage changes were recorded: TC-31%, LDL-C - 35%, VLDL-C-51%, HDL-C+20%, TG-47%, apoprotein B-34%, apoprotein A-I+1 1%, LDL-C to HDL-C ratio -45%, and apoprotein B to A-I ratio -41%. The relative risk of MI was reduced by 58%. All changes were significant (p < 0.001). No patient was withdrawn from die study because of treatm ent-induced adverse effects. Five patients exhibited a moderate transi ent serum enzyme elevation: 2 in creatinine kinase and 3 in transamina se. Myopathy or rhabdomyolysis, major gastrointestinal symptoms, deter ioration of renal function, or insomnia were not recorded in any patie nts. Combined treatment with gemfibrozil and pravastatin is safe and e ffective, but should be administered only in selected patients with se vere combined hyperlipidaemia.