Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia

Summary The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe hypercholesterolaemia.After 6 weeks of treatment the simvastatin group showed a significantly greater (p<0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL₂ and HDL₃ cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively.The mean plasma apolipoprotein A–I concentration was significantly higher only on simvastatin treatment.Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum alanine aminotransferase (S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range.It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of hypercholesterolaemia. Simvastatin was also better tolerated and it is more convenient for patients to take.