Cholesterol levels after 3 days of high-dose simvastatin in patients at moderate to high risk for coronary events

Background: Elevated levels of low-density lipoprotein cholesterol (LDL-C) impair vascular function by a variety of mechanisms. HMG CoA reductase inhibitors (statins) improve endothelial function by lowering LDL-C and possibly by other "pleiotropic" effects. How rapidly statins can lower LDL-C has not been thoroughly studied. Methods: We examined the lipid response to 3 days of high-dose simvastatin in a randomized prospective double-blind placebo-controlled crossover study. Twenty-seven subjects at moderate to high risk for coronary heart disease (CHD) received either simvastatin 80 mg/day for 3 days followed by placebo for 3 days or placebo followed by simvastatin. After a washout period of 10 to 14 days, subjects received the opposite treatment. Nonfasting blood lipid levels, including total cholesterol, direct LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides, were obtained before randomization and after each 3-day treatment period. Results: The mean LDL-C level at baseline was 107 mg/dl and decreased 24% in patients receiving simvastatin and 5.6% in patients receiving placebo (P<0.001). Statistically significant reductions were also achieved in the total cholesterol and cholesterol/HDL-C ratio: 14% and 12%, respectively. Changes in HDL-C and triglyceride levels were not significant. Conclusion: Treatment with simvastatin for only 3 days results in a 24% drop in the LDL-C level. As defined by ATPIII, this decrease is comparable to that necessary to lower the LDL-C from one risk level to a lower one and is, therefore, both clinically and statistically significant.