BACKGROUND: Hypercholesterolemia, a common problem after heart transplantation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare the efficacy of gemfibrozil, simvastatin, and cholestyramine for cholesterol lowering in heart transplant recipients. METHODS: In this prospective 1-year study, 48 heart transplant recipients with moderate hypercholesterolemia were randomized to therapy with gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was performed at baseline and after 3, 6, and 12 months of treatment. RESULTS:Total cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%, respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained reduction in total cholesterol (25%) and low-density lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at the end of 1 year with simvastatin but not with the other treatments. Serum triglyceride levels were reduced significantly by treatment with gemfibrozil (up to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and gemfibrozil; however, this effect did not persist to 12 months. However, the ratio of low-density lipoprotein/high-density lipoprotein was favorably 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 and ten from the cholestyramine arm. Gastrointestinal intolerance was the most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No biochemical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels. CONCLUSIONS: Of the three therapies studied, simvastatin was found to be the most efficacious and well tolerated for cholesterol lowering in patients after heart transplantation.
RCT Entities:
BACKGROUND:Hypercholesterolemia, a common problem after heart transplantation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare the efficacy of gemfibrozil, simvastatin, and cholestyramine for cholesterol lowering in heart transplant recipients. METHODS: In this prospective 1-year study, 48 heart transplant recipients with moderate hypercholesterolemia were randomized to therapy with gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was performed at baseline and after 3, 6, and 12 months of treatment. RESULTS: Total cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%, respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained reduction in total cholesterol (25%) and low-density lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at the end of 1 year with simvastatin but not with the other treatments. Serum triglyceride levels were reduced significantly by treatment with gemfibrozil (up to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and gemfibrozil; however, this effect did not persist to 12 months. However, the ratio of low-density lipoprotein/high-density lipoprotein was favorably 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 and ten from the cholestyramine arm. Gastrointestinal intolerance was the most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No biochemical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels. CONCLUSIONS: Of the three therapies studied, simvastatin was found to be the most efficacious and well tolerated for cholesterol lowering in patients after heart transplantation.
Authors: Tuire Tirkkonen; Anna Ryynänen; Tero Vahlberg; Kerttu Irjala; Timo Klaukka; Risto Huupponen; Kari Laine Journal: Drug Saf Date: 2008 Impact factor: 5.606