CHOLESTEROL-LOWERING THERAPY AFTER HEART-TRANSPLANTATION - A 12-MONTHRANDOMIZED TRIAL

Background: Hypercholesterolemia, a common problem after heart transpl antation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare t he efficacy of gemfibrozil, simvastatin, and cholestyramine for choles terol lowering in heart transplant recipients. Methods: In this prospe ctive 1-year study, 48 heart transplant recipients with moderate hyper cholesterolemia were randomized to therapy with gemfibrozil 600 mg twi ce daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramin e 4 gm twice daily (n = 18). Detailed lipoprotein analysis was perform ed at baseline and after 3, 6, and 12 months of treatment. Results: To tal cholesterol and low-density lipoprotein cholesterol were reduced 1 9% and 29%, respectively, after 3 months of simvastatin therapy (p < 0 .0001) with a sustained reduction in total cholesterol (25%) and low-d ensity lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and choles tyramine treatment did not result in a reduction in cholesterol levels . Apolipoprotein B levels were reduced by 29% at the end of 1 year wit h simvastatin but not with the other treatments. Serum triglyceride le vels were reduced significantly by treatment with gemfibrozil (up to 3 6%,p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and g emfibrozil; however, this effect did not persist to 12 months. However , the ratio of low-density lipoprotein/high-density lipoprotein was fa vorably affected by simvastatin, with a 38% reduction by 12 months (p < 0.0001) but not by the other treatments. Over the course of 1 year, 14 patients dropped out of the study: four from the gemfibrozil arm an d ten from the cholestyramine arm. Gastrointestinal intolerance was th e most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No bioch emical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels. Conclusions: Of t he three therapies studied, simvastatin was found to be the most effic acious and well tolerated for cholesterol lowering in patients after h eart transplantation.