Pravastatin, cholestyramine and gemfibrozil in long-term therapy of primary hypercholesterolemia. An open randomized comparative study

In this open controlled clinical trial the lipid-lowering effect, the tolerance and clinical safety of the new hydrophilic HMG-CoA reductase inhibitor pravastatin and cholestyramine were compared in the treatment of 45 patients with primary hypercholesterolaemia over a period of 16 weeks. Following a dietary lead-in of six weeks, patients were randomized at a ratio of 3:2 to receive either pravastatin 10 mg b.i.d. or cholestyramine 8 g b.i.d. The dose of pravastatin was increased to 40 mg per day after eight weeks of treatment and after 16 weeks cholestyramine 8 g b.i.d. was added. Two thirds of the patients in the cholestyramine group were switched to gemfibrocil 900 mg. At the end of the 48 week treatment period the mean reduction rates of total cholesterol, LDL-cholesterol and triglycerides for the pravastatin combination compared to cholestyramine (in brackets values for gemfibrocil) were -30, -35 and -17% versus -17 (-19), -25 (-22) and +27 (-24)%. Pravastatin lead to an increase of the HDL concentration of approximately 8%, gemfibrocil to approximately 13%, whilst cholestyramine alone did not change this lipid fraction. The reduction of total cholesterol and LDL-cholesterol was associated with a decrease in the apolipoprotein B concentration. However, the apolipoprotein AI and AII levels remained unchanged. Due to the absence of clinically relevant side effects and laboratory abnormalities coupled with the excellent compliance in this study, pravastatin proved to be a convincing therapeutic alternative to cholestyramine and gemfibrocil. The combination therapy of pravastatin and cholestyramine offers a potentially highly efficacious and safe therapeutic regimen for the future.