Effects of statins on high-density lipoproteins: a potential contribution to cardiovascular benefit.

Purpose: The objective was to systematically review clinical trial data on the effects of statins on high-density lipoproteins (HDL) and to examine the possibility that this provides cardiovascular benefits in addition to those derived from reductions in low-density lipoproteins (LDL).

Methods: The PubMed database was searched for publications describing clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin. On the basis of predefined criteria, 103 were selected for review.

Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high-density lipoproteins.

Atorvastatin and rosuvastatin are both highly effective in decreasing low-density lipoprotein cholesterol and triglyceride levels. However, rosuvastatin was shown to be more effective in increasing high-density lipoprotein (HDL) cholesterol levels. The purpose of the study is to compare the effects of daily doses of rosuvastatin 40 mg with atorvastatin 80 mg during a 6-week period on HDL subpopulations in 306 hyperlipidemic men and women.

Effect of short-term rosuvastatin treatment on estimated glomerular filtration rate.

To define the effect of short-term rosuvastatin treatment on the estimated glomerular filtration rate (eGFR), the database of controlled clinical trials in the Rosuvastatin Clinical Development Program was reviewed. Thirteen studies comprising 3,956 rosuvastatin-treated patients were selected based on a serum creatinine measurement at 6 or 8 weeks after initiation of rosuvastatin treatment, randomization to approved and marketed rosuvastatin doses (5 to 40 mg), and unchanged rosuvastatin dose from treatment initiation (baseline) through 6 to 8 weeks of treatment. eGFR was determined with the Modification of Diet in Renal Disease formula.

Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells.

Renal proximal tubule cells are responsible for the reabsorption of proteins that are present in the tubular lumen. This occurs by receptor-mediated endocytosis, a process that has a requirement for some GTP-binding proteins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase used for the therapeutic reduction of cholesterol-containing plasma lipoproteins.

Phenotype-dependent and -independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia.

This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and hypertriglyceridaemic (HTG, n = 16; TG > or = 2.

Comparative pharmacology of rosuvastatin.

The major therapeutic action of statin drugs is reduction in levels of circulating atherogenic lipoproteins as a result of inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mainly in the liver. The magnitude of reduction of atherogenic lipoproteins differs among various statins. It is suggested that an ideal statin would maximize the pharmacodynamic activity in the liver and minimize the inhibitory activity outside the liver, particularly in some vulnerable tissues, such as skeletal muscle.

New dimension of statin action on ApoB atherogenicity.

Newer, more effective statins are powerful agents for reducing elevated levels of low-density lipoprotein (LDL) cholesterol and thereby lowering the risk of coronary heart disease (CHD) and related adverse events. Although LDL remains the primary target of therapy for reducing CHD risk, increased interest is focusing on apolipoprotein B (apoB)-containing lipoprotein subfractions--particularly very-low-density lipoprotein (VLDL). VLDL remnants, and intermediate-density lipoproteins (IDL)--as secondary targets of therapy.

Rosuvastatin: a highly effective new HMG-CoA reductase inhibitor.

Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG-CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome p450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug-drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose-ranging studies in hypercholesterolemic patients demonstrated dose-dependent effects in reducing low-density lipoprotein cholesterol (LDL-C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1- to 40-mg dose range and a significant 8.

Optimizing the pharmacology of statins: characteristics of rosuvastatin.

Rosuvastatin (Crestor, AstraZeneca) is a new synthetic statin that exhibits a number of highly desirable pharmacologic characteristics. The drug has a high affinity for the active site of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and exhibits greater potency in inhibiting enzyme activity and cholesterol synthesis in vitro than other statins. The effects of rosuvastatin are selective for hepatic cells, and there is minimal uptake of the drug by nonhepatic tissues.