pitavastatin and Myocardial-Ischemia

This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear.. The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin.. The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371).. Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.

Topics: Aged; Biomarkers; Cholesterol, LDL; Down-Regulation; Dyslipidemias; Exercise Tolerance; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Ischemia; Pravastatin; Prospective Studies; Quinolines; Recovery of Function; Republic of Korea; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS).. Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated.. This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.

Topics: Atorvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Myocardial Ischemia; Pyrroles; Quinolines; Research Design; Syndrome

Incomplete recovery of myocardial contraction after reperfusion following brief ischemia is called the "stunning phenomenon" in an animal experiment. A hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) does not affect this phenomenon, but lipophilic statins further reduce the contraction during reperfusion. The effects of novel hydrophilic rosuvastatin and lipophilic pitavastatin on myocardial stunning in dogs were examined. In a preliminary experiment in vitro, pitavastatin reduced L6 cell viability at 10(-6) M and higher, whereas rosuvastatin and pravastatin up to 10(-5) M did not show such effects. An empty capsule or a capsule filled with rosuvastatin (2 mg/kg per day) or pitavastatin (0.4 mg/kg per day) was orally administered to dogs. After 3 weeks, both statins lowered the serum cholesterol level to the same extent. Under pentobarbital anesthesia, dogs were subjected to 15-min ischemia followed by 120-min reperfusion. Ischemia arrested the myocardial contraction in the ischemic area, and reperfusion recovered it but incompletely, showing the stunning phenomenon. Rosuvastatin did not modify the stunning phenomenon, while pitavastatin further deteriorated the myocardial contraction during reperfusion.

Topics: Administration, Oral; Animals; Cell Line; Cell Survival; Cholesterol; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Energy Metabolism; Female; Fluorobenzenes; Hemodynamics; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Muscle, Skeletal; Myocardial Contraction; Myocardial Ischemia; Myocardial Stunning; Myocardium; Pyrimidines; Quinolines; Rats; Rosuvastatin Calcium; Sulfonamides; Time Factors