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

• Published in: International journal of cardiology Vol. 94; no. 1; pp. 111 - 117
• Main Authors: Sakabe, Koichi, Fukuda, Nobuo, Wakayama, Katsunori, Nada, Teru, Shinohara, Hisanori, Tamura, Yoshiyuki
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.03.2004; Elsevier Science
• Subjects: Acute coronary syndromes; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticholesteremic Agents - therapeutic use; Atorvastatin Calcium; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Disorders of blood lipids. Hyperlipoproteinemia; Female; Heart; Heptanoic Acids - therapeutic use; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Lipid profile; Lipoproteins - blood; Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation; Phenotype; Pleiotropic effects; Pyridines - therapeutic use; Pyrroles - therapeutic use; Statins; Time Factors; Lipid profile; Acute coronary syndromes; Pleiotropic effects; Statins; Human; Acute; Metabolic diseases; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Statin derivative; Time; Lipoprotein; Coronary heart disease; Cholesterol; Profile; Hypercholesterolemia; Dyslipemia; Comparative study
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2003.08.001

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.