Time course differences for statin-induced pleiotropic effects in hypercholesterolemic patients

Background: It is unclear whether there are temporal differences for the pleiotropic effects for different members of the statin class. The present study investigated differences in the short- and intermediate-term pleiotropic effects of statins in hypercholesterolemic patients. Methods: Thirty-five hypercholesterolemic patients were randomly treated with either atorvastatin or cerivastatin for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) at baseline and after 2 weeks and 3 months of therapy. Results: After 2 weeks of therapy, atorvastatin decreased the low density lipoprotein (LDL) cholesterol, small, dense LDL cholesterol (34±22 vs. 18±20%, P<0.01), remnant-like particles (RLP) cholesterol (8.8±6.0 vs. 5.1±2.6 mg/ml, P<0.01), and TBARS (3.3±1.0 vs. 3.1±0.9 nmol/ml, P<0.05), and cerivastatin decreased LDL cholesterol. After 3 months of therapy, atorvastatin decreased small dense LDL cholesterol (8±13%, P<0.0001) additionally, and cerivastatin decreased small, dense LDL cholesterol (51±11 vs. 12±22%, P<0.0001) and plasminogen activator inhibitor type 1 (68±32 vs. 51±21 ng/ml, P<0.05). FMD increased significantly in both groups after 2 weeks, although the relative change in FMD was greater with cerivastatin therapy after 2 weeks than atorvastatin therapy (60±78 vs. 23±26%, P<0.05). However, FMD was the same for both groups after 3 months (58±65 vs. 66±61%, NS), because atorvastatin additionally increased FMD. There was no correlation between these pleiotropic effects and the improvement in the lipid profile for either group. Conclusions: These findings suggest that the degree of pleiotropic effect as well as the time course for the effect are different among members of the statin class of drugs.