pitavastatin and Kidney-Diseases

Our study aims to evaluate the efficacy and safety of long-term treatment of statins for coronary heart disease (CHD).. Efficacy outcomes included changes in blood lipids, risk of CHD mortality and all-cause mortality. Safety outcomes were evaluated by the risk of adverse events (AE). Bayesian network meta-analysis was used to compare the direct and indirect effects between different statins.. The systematic review showed that levels of blood lipids decreased during statin treatment. High dose of atorvastatin was the most obvious treatment for the reduction of blood lipids. Network meta-analysis showed that statins were significantly more effective than the control in reducing the risk of CHD mortality (Odds Ratio (OR) 0.69, 95% CI 0.61-0.77) and all-cause mortality (OR 0.84, 95% CI 0.80-0.87). In terms of reducing the risk of CHD morality, fluvastatin (77.3%), atorvastatin (72.3%) and lovastatin (68.4%) had higher cumulative probability than other statins, which were more effective treatments for the reduction of CHD morality. In terms of reducing all-cause mortality, atorvastatin (78.6%), fluvastatin (77.1%) and pitavastatin (74.1%) had higher cumulative probability than other statins, which were more effective treatment for reducing the all-cause mortality. Compared with placebo, statins increased the incidence risk of muscle disease (OR 1.05, 95% CI 1.00-1.10) and kidney disease (OR 1.11, 95% CI 1.05-1.72).. Statins significantly reduced levels of blood lipids, with a high dose of atorvastatin being the most effective in blood-lipid level modification. Statins reduced the risk of CHD mortality and all-cause mortality, with atorvastatin and fluvastatin being the most effective in reducing the risk of CHD mortality and all-cause mortality. Statins increased the risk of muscle disease and kidney damage.

Topics: Anticholesteremic Agents; Atorvastatin; Bayes Theorem; Coronary Disease; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Diseases; Lipids; Lovastatin; Muscles; Network Meta-Analysis; Patient Safety; Pravastatin; Quinolines; Randomized Controlled Trials as Topic; Simvastatin; Treatment Outcome

Although clinical trials provide useful information on drug safety and efficacy, results do not always reflect those observed in the real world. The Japanese long-term prospective post-marketing surveillance LIVALO Effectiveness and Safety (LIVES) Study was designed to assess the efficacy and safety of pitavastatin in clinical practice in ~20,000 patients. After 104 weeks, pitavastatin was associated with significant reductions in low-density lipoprotein-cholesterol (LDL-C) (29.1%) that largely occurred within 4 weeks of treatment initiation. In patients with abnormal triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) levels at baseline, pitavastatin reduced TG and increased HDL-C by 22.7% and 19.9%, respectively. Overall, 88.2% of the primary prevention low-risk patients attained their Japan Atherosclerosis Society LDL-C target, compared with 82.7% of intermediate-risk patients, 66.5% of high-risk patients and 50.3% of secondary prevention patients. Only 10.4% of pitavastatin-treated patients experienced adverse events (AEs), of which approximately 84% were mild and around 1% was severe. Increases in blood creatine phosphokinase (2.7%), alanine aminotransferase (1.8%), myalgia (1.1%), aspartate aminotransferase (1.5%) and gamma-glutamyltransferase (1.0%) were the most common AEs and only 7.4% of patients discontinued pitavastatin due to AEs. Regression analysis demonstrated that age was not a significant factor for the incidence of any AE or myopathy-associated events. A subanalysis of initial LIVES data focussing on the effects of pitavastatin on HDL-C levels showed that HDL-C was elevated by 5.9% in all patients and by 24.6% in those with low (

Topics: Atorvastatin; Biomarkers; Cardiovascular Diseases; Cerebrovascular Disorders; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase IV as Topic; Comorbidity; Diabetes Mellitus, Type 2; Dyslipidemias; Glomerular Filtration Rate; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kidney Diseases; Multicenter Studies as Topic; Muscular Diseases; Prospective Studies; Pyrroles; Quinolines; Risk; Simvastatin; Treatment Outcome; Triglycerides

Renal dysfunction is an independent risk factor for cardiovascular events. However, little is known regarding the impacts of renal dysfunction on coronary atherosclerosis.. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the TRUTH study using virtual histology intravascular ultrasound in 164 patients with angina pectoris. We analyzed correlations between the estimated glomerular filtration rate (eGFR) and coronary atherosclerosis before and during statin therapy.. Baseline eGFR was 64.5 mL/min per 1.73 m(2) . Serum low-density lipoprotein cholesterol level decreased significantly from 132 to 85 mg/dL (-35%, P < 0.0001) after 8 months. Weak, but significant, negative correlations were observed between eGFR and external elastic membrane volume (r = -0.228, P = 0.01) and atheroma volume (r = -0.232, P = 0.01) at baseline. The eGFR was also negatively correlated with fibro-fatty volume (r = -0.254, P = 0.005) and fibrous volume (r = -0.241, P = 0.008) at baseline. Multivariate regression analyses showed that eGFR was a significant independent predictor associated with statin pre-treatment volume in fibro-fatty (β = -0.23, P = 0.01) and fibrous (β = -0.203, P = 0.02) components. Furthermore, eGFR was positively correlated with volume change in the fibro-fatty component during statin therapy (r = 0.215, P = 0.02).. Decreased eGFR is associated with expanding remodelling and a greater atheroma volume, particularly the fibro-fatty and fibrous volume before statin therapy in patients with normal to mild renal dysfunction. Reduction of fibro-fatty volume during statin therapy gradually accelerated with decreasing renal function.

Topics: Aged; Biomarkers; Coronary Artery Disease; Coronary Vessels; Dyslipidemias; Female; Fibrosis; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kidney; Kidney Diseases; Lipids; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Since co-administration of ezetimibe, a specific inhibitor of cholesterol absorption into the intestine, has been shown to augment lipid-lowering effects of statins, ezetimibe plus statins is a novel therapeutic strategy for the treatment of dyslipidemia in high-risk patients. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease (CKD). However, effects of co-administration of ezetimibe with statins on renal damage and dysfunction in CKD patients remain unknown. In this study, we examined whether co-administration of ezetimibe with pitavastatin could augment renoprotective properties of pitavastatin in non-diabetic CKD patients with dyslipidemia. Total cholesterol, LDL-cholesterol and triglycerides levels were reduced more by co-administration of ezetimibe (10mg/day) with pitavastatin (2mg/day) (n=10) than by pitavastatin alone (n=10). In addition, ezetimibe plus pitavastatin treatment produced significant incremental reduction in proteinuria related to pitavastatin therapy alone. In univariate analyses, proteinuria was correlated with plasma levels of total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely), asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and urinary excretion levels of L-fatty acid binding protein (L-FABP), a marker of tubular injury and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker. Multiple stepwise regression analysis revealed that LDL-cholesterol (p<0.001) and urinary excretion levels of L-FABP (p=0.001) and 8-OHdG (p<0.001) were independently related to proteinuria (R(2)=0.969). Our present study demonstrated for the first time that co-administration of ezetimibe enhanced proteinuria-lowering effects of pitavastatin in non-diabetic CKD patients partly via a cholesterol-independent manner. Ezetimibe may have pleiotropic actions that could contribute to renoprotective properties of this lipid-lowering agent.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anticholesteremic Agents; Arginine; Azetidines; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Deoxyguanosine; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Fatty Acid-Binding Proteins; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Male; Middle Aged; Proteinuria; Quinolines; Severity of Illness Index; Treatment Outcome; Triglycerides

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

We attempted to elucidate the relationship between cholesterol absorption and kidney damage by investigating the renoprotective effect of ezetimibe, a cholesterol absorption inhibitor, in 5/6 nephrectomized rats (Nx). The Nx or sham-operated rats (Sham) were fed 1% high-cholesterol diet (HC) containing ezetimibe (10 mg/[kg d]), pitavastatin (3 mg/[kg d]), or both for 8 weeks. Pathological changes, endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA), and oxidative stress were assessed in the kidney. The Sham fed HC exhibited hypercholesterolemia and glomerulosclerosis with macrophage infiltration in the kidney, and ezetimibe attenuated these changes. The Nx exhibited hypercholesterolemia, increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), glomerulosclerosis with macrophage infiltration and interstitial fibrosis, and downregulation of eNOS mRNA. The HC increased cholesterol further and worsened the kidney damage with increased 8-OHdG. Ezetimibe attenuated the hypercholesterolemia, kidney dysfunction, and pathological changes. The beneficial effects of ezetimibe were significantly associated with reduced 8-OHdG (P < .01). Pitavastatin did not reduce cholesterol or 8-OHdG, but it did significantly suppress the kidney damage with upregulated eNOS mRNA by 2.5-fold (P < .02). The combination of ezetimibe and pitavastatin synergistically ameliorated the kidney damage. The kidney dysfunction and pathological changes were significantly associated with cholesterol, markers of cholesterol absorption (campesterol and cholestanol), and 8-OHdG (P < .001-.05). Multiple regression analysis revealed that the markers of cholesterol absorption were independently associated with the kidney damage. Ezetimibe confers renoprotective effects by inhibiting cholesterol absorption, which in turn reduces oxidative stress; and pitavastatin additively ameliorates kidney damage by increasing NO production via mechanisms independent of cholesterol reduction.

Topics: Animals; Anticholesteremic Agents; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Azetidines; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Creatinine; Deoxyguanosine; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Function Tests; Male; Nephrectomy; Proteinuria; Quinolines; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA; Triglycerides