Efficacy and safety of Simvastatin for high-risk hypercholesterolemia

Ten years' experience of treatment with the 3-hydroxy-methylglutaryl coenzy me A reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk p atients is reported. All patients started with 20 mg simvastatin/day, The s imvastatin dose was increased to 40 mg in 22 patients. Fourteen patients ne eded further addition of cholestyramine, Simvastatin reduced plasma cholest erol by 33% after 1 month and was further reduced after adjustment of the l ipid-lowering treatment, The mean reduction in plasma cholesterol varied be tween 30% and 35% in 2 to 10 years. Low-density lipoprotein cholesterol dem onstrated mean reductions of 34% to 42%, Mean plasma triglycerides were red uced by 26% after 1 month and by 1% to 19% the following years. High-densit y lipoprotein (HDL) cholesterol increased initially by 8% and remained elev ated at 7% to 11% during the first 6 years, but then dropped slightly below baseline. HDL2 cholesterol increased by 9% to 25% the first 6 years and th en decreased. HDL3 cholesterol showed a persistent elevation during simvast atin treatment. About half of the subjects had minor transient but clinical insignificant increases in creatine kinase. No cases of myopathy were seen . Mean serum aspartate aminotransferase and alanine aminotransferase increa sed significantly but within the normal ranges during the 10 years. The tol erability and compliance of simvastatin treatment wets excellent as judged from patients' reports and from analyses of low-density lipoprotein cholest erol, This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long -term treatment of hypercholesterolemic patients at risk. (C) 1999 by Excer pta Medica, Inc.