pitavastatin and Chronic-Disease

Recent clinical trials using rosuvastatin, a hydrophilic statin, did not show beneficial effects on cardiovascular events in patients with heart failure. We examined the cardioprotective effects of pitavastatin, a lipophilic statin, on Japanese patients with chronic heart failure (CHF).. A total of 574 Japanese patients with CHF were randomly assigned to the pitavastatin group (n=288) or the control group (n=286). There was no significant difference between the 2 groups for the primary outcome, which was a composite of cardiac death and hospitalization for worsening HF (adjusted hazard ratio (aHR): 0.922, 95% confidence interval (CI): 0.632-1.345, P=0.672). A strongly significant statistical interaction between the effect of pitavastatin and left ventricular ejection fraction (LVEF) was found (P=0.004). In patients with LVEF ≥30%, a significant reduction in the primary outcome (aHR: 0.525, 95% CI: 0.308-0.896, P=0.018) was observed in the pitavastatin group. Pitavastatin did not show any effects on the primary outcome (aHR: 1.582, 95% CI: 0.890-2.813, P=0.118) in the subgroup of patients with LVEF <30%.. Pitavastatin did not reduce cardiac death or hospitalization for worsening HF in Japanese patients with CHF. (UMIN-ID: UMINC000000428).

Topics: Aged; Asian People; Cardiotonic Agents; Chronic Disease; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Prospective Studies; Quinolines; Stroke Volume

HMG-CoA reductase inhibitors (statins) are known to have pleiotropic effects in addition to their lipid-lowering effect. Many studies have suggested cardioprotective effects of statins, however, recent large-scale clinical trials using rosuvastatin, a hydrophilic statin, have failed to show beneficial effects on cardiovascular events in patients with severe heart failure. We have designed the study to evaluate the effects of pitavastatin, a lipophilic statin, on Japanese patients with mild to moderate heart failure.. Five hundred seventy-seven patients with chronic heart failure were enrolled. We used a prospective, randomized, open-label, and blinded-endpoint evaluation (PROBE) design. Patients aged 20-79 years old with symptomatic (NYHA functional class II or III) heart failure and a left ventricular ejection fraction of ≤ 45% were randomly allocated to either receive pitavastatin (2mg/day) or not in addition to conventional therapy for heart failure by using the minimization method. Follow-up will be continued until March 2011. The primary endpoint is a composite of cardiac death and hospitalization for worsening heart failure.. The PEARL study will provide important data on the role of pitavastatin in the treatment of Japanese patients with mildly symptomatic heart failure (UMIN-ID: UMINC000000428).

Topics: Aged; Asian People; Chronic Disease; Death; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Prospective Studies; Quinolines; Treatment Outcome

Urinary liver-type fatty-acid-binding protein (L-FABP) is a useful clinical marker in the monitoring of chronic kidney disease (CKD) associated with tubulointerstitial damage. Statins have been shown to be effective in the treatment of renal disease. The aim of the present study was to determine whether pitavastatin, a newly developed statin, modulates the urinary L-FABP levels in normolipidemic patients with CKD.. Thirty normolipidemic mild CKD patients (18 males and 12 females, mean age 40 years, mean serum creatinine level 1.0 mg/dl) were randomly assigned to two groups: (1) pitavastatin (1 mg/day, n = 15) and (2) placebo (n = 15). Urinary protein and urinary L-FABP levels were measured before the initiation of treatment and 3 and 6 months thereafter. Twenty age-matched healthy subjects were also studied as controls.. Before treatment, the urinary L-FABP levels in 30 CKD patients (84.0 +/- 68.5 microg/g creatinine) were significantly higher than those of healthy subjects (6.4 +/- 4.2 mug/g creatinine; p < 0.001). Pitavastatin slightly reduced serum total cholesterol and triglyceride levels, but this was not statistically significant. However, pitavastatin reduced the urinary protein excretion from 1.8 to 1.0 g/day (p < 0.01), while the urinary L-FABP levels fell from 88.5 +/- 70.5 to 28.0 +/- 16.5 mug/g creatinine (p < 0.01).. The present data suggest that pitavastatin ameliorates tubulointerstitial damage in CKD patients independent of the lipid-lowering effect.

Topics: Adult; Biomarkers; Cholesterol; Chronic Disease; Fatty Acid-Binding Proteins; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Male; Proteinuria; Quinolines; Triglycerides

Topics: Anti-Inflammatory Agents; Antioxidants; Atorvastatin; Cell Proliferation; Chronic Disease; Dinoprostone; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Inflammation; Interleukin-1beta; Lipids; Lipopolysaccharides; Microglia; Monocytes; Nitric Oxide; Pravastatin; Quinolines; Reactive Oxygen Species; Rosuvastatin Calcium; Simvastatin; THP-1 Cells; Tumor Necrosis Factor-alpha

We recently demonstrated in a murine model that nanoparticle-mediated delivery of pitavastatin into vascular endothelial cells effectively increased therapeutic neovascularization. For the development of a clinically applicable approach, further investigations are necessary to assess whether this novel system can induce the development of collateral arteries (arteriogenesis) in a chronic ischemia setting in larger animals.. Chronic hind limb ischemia was induced in rabbits. They were administered single injections of nanoparticles loaded with pitavastatin (0.05, 0.15, and 0.5 mg/kg) into ischemic muscle.. Treatment with pitavastatin nanoparticles (0.5 mg/kg), but not other nanoparticles, induced angiographically visible arteriogenesis. The effects of intramuscular injections of phosphate-buffered saline, fluorescein isothiocyanate (FITC)-loaded nanoparticles, pitavastatin (0.5 mg/kg), or pitavastatin (0.5 mg/kg) nanoparticles were examined. FITC nanoparticles were detected mainly in endothelial cells of the ischemic muscles for up to 4 weeks. Treatment with pitavastatin nanoparticles, but not other treatments, induced therapeutic arteriogenesis and ameliorated exercise-induced ischemia, suggesting the development of functional collateral arteries. Pretreatment with nanoparticles loaded with vatalanib, a vascular endothelial growth factor receptor (VEGF) tyrosine kinase inhibitor, abrogated the therapeutic effects of pitavastatin nanoparticles. Separate experiments with mice deficient for VEGF receptor tyrosine kinase demonstrated a crucial role of VEGF receptor signals in the therapeutic angiogenic effects.. The nanotechnology platform assessed in this study (nanoparticle-mediated endothelial cell-selective delivery of pitavastatin) may be developed as a clinically feasible and promising strategy for therapeutic arteriogenesis in patients.

Topics: Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Animals; Cells, Cultured; Chronic Disease; Collateral Circulation; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Electric Stimulation; Endothelial Cells; Feasibility Studies; Hindlimb Suspension; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Injections, Intramuscular; Ischemia; Male; Mice; Mice, Knockout; Mice, Transgenic; Muscle, Skeletal; Nanoparticles; Neovascularization, Physiologic; Oxygen; Phthalazines; Protein Kinase Inhibitors; Pyridines; Quinolines; Rabbits; Regional Blood Flow; Time Factors; Vascular Endothelial Growth Factor Receptor-1

HMG-CoA reductase inhibitors play several roles in the maintenance of organ transplants. We investigated the role of pitavastatin, a potent and newly developed HMG-CoA reductase inhibitor, in cardiac allograft rejection and mechanism of graft arterial disease (GAD) suppression.. Balb/c mice hearts were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2()KhEg (a class II mismatch combination) to examine the extent of GAD. Pitavastatin was administered orally to mice everyday (3 mg/kg/day). To assess the effect in acute rejection, mixed lymphocyte reaction was performed and cytokine mRNA expression was examined with ribonuclease protection assay.. Pitavastatin significantly prolonged allograft survival. Lymphocyte proliferation was inhibited by pitavastatin, and RPA showed down-regulation of interleukin-6 in pitavastatin-treated cardiac allografts. Allografts in the pitavastatin-treated group after 8 weeks showed less GAD compared with the control group. In vitro, pitavastatin suppressed the smooth muscle cell proliferation in response to activated T cells and inhibited extracellular signal-regulated kinase 1/2 activation.. Pitavastatin could be effective in the suppression of acute rejection and GAD development in cardiac transplantation.

Topics: Acute Disease; Animals; Cell Proliferation; Cholesterol; Chronic Disease; Cytokines; Gene Expression Regulation; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Lymphocyte Culture Test, Mixed; Male; Mice; Myocytes, Smooth Muscle; Quinolines; Spleen; Survival Rate; Transplantation, Homologous; Triglycerides