pitavastatin and Hypercholesterolemia

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are administered as first line therapy for hypercholesterolemia, both in primary and secondary prevention. There is a growing body of evidence showing that beyond their lipid-lowering effect, statins have a number of additional beneficial properties. Pitavastatin is a unique lipophilic statin with a strong effect on lowering plasma total cholesterol and triacylglycerol. It has been reported to have pleiotropic effects such as decreasing inflammation and oxidative stress, regulating angiogenesis and osteogenesis, improving endothelial function and arterial stiffness, and reducing tumor progression. Based on the available studies considering the risk of statin-associated muscle symptoms it seems to be also the safest statin. The unique lipid and non-lipid effects of pitavastatin make this molecule a particularly interesting option for the management of different human diseases. In this review, we first summarized the lipid effects of pitavastatin and then strive to unravel the diverse pleiotropic effects of this molecule.

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Quinolines

Statins are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market. Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a recent cardiovascular outcome study. Expert opinion: Pitavastatin produces dose-dependent reductions in LDL-C at lower doses than other statins. The maximum approved dose of 4 mg reduces LDL-C by about 40-49% in different patient groups and is equivalent to atorvastatin 20 mg in this effect. Pitavastatin undergoes minimal metabolism so drug-drug interactions are less likely than with many other statins, but it can interact with some drugs that inhibit drug transporters. Compared with other statins, it has been associated with greater increases in high-density lipoprotein cholesterol and it was found to be less likely to cause new onset diabetes. In a recent study in Japanese patients with stable coronary artery disease, pitavastatin 4 mg was more effective than pitavastatin 1 mg in reducing cardiovascular events. Therefore, the highest dose may be preferred in high-risk patients.

Topics: Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Treatment Outcome

In short-term, phase III or IV studies in Asian and European patients, pitavastatin 1, 2 and 4 mg once daily reduced LDL-Cholesterol (LDL-C) 34%, 42% and 47%, respectively. Pitavastatin provided sustained LDL-C-lowering efficacy over up to 60 weeks' therapy in extension studies. In comparative studies pitavastatin 4 mg and simvastatin 40 mg reduced LDL-C similarly, reduction in triglycerides and increase in HDL-Cholesterol (HDL-C) was more prominent with pitavastatin. In comparative studies with atorvastatin, pitavastatin 4mg was found to be more effective than 20 mg of atorvastatin, and a little less effective than 40 mg of atorvastatin. The increase in HDL-C demonstrated in short term studies sustained in long term, whereas with atorvastatin the increase in HDL-C was less prominent. Pitavastatin was generally well tolerated in these studies and most treatment emergent adverse events were mild or moderate and their frequency was not different from other statins. Pitavastatin did not appear to adversely affect glucose metabolism parameters (e.g. fasting blood glucose, fasting plasma insulin, glycated hemoglobin) in short- and longer-term prospective and post-marketing surveillance studies in adults. In conclusion, pitavastatin is an effective treatment option in adults with primary hypercholesterolemia and combined (mixed) dyslipidemia, including those at risk of developing type 2 diabetes.

Topics: Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

HMG-CoA reductase inhibitors (statins) represent the most effective class of LDL lowering drugs with an overall positive safety and tolerability profile. They have also consistent benefit in terms of reduced cardiovascular (CV) events in both primary and secondary prevention. Pitavastatin is a new member of the statin class. This review provides a current overview of pravastatin's role in CV risk reduction. In brief pitatastatin has pleitrophic effects as the other statins. It has been shown that it reduces plaque atheroma volume in acute coranary settings. Also the 'real life' evidence gained with pitavastatin in LIVES study, a longterm postmarketing surveillance study in more than 20,000 patients in Japan, denotes an effective CV risk reduction with this new statin.

Topics: Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Plaque, Atherosclerotic; Quinolines

Oral pitavastatin (Livalo

Topics: Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Despite attaining LDL-cholesterol targets, many patients with diabetes remain at risk of developing cardiovascular events. In addition, treatment with statins has been associated with a slight but significant increased risk of development of diabetes, particularly with high-intensity statins. Pitavastatin is a moderate- to high-intensity statin that effectively reduces LDL-cholesterol levels. Pitavastatin provides a sustained increase of HDL-cholesterol levels that may exhibit a neutral or positive effect on glucose metabolism, may not increase the risk of new-onset diabetes, may exhibit positive effects on renal function and urinary albumin excretion and the risk of drug-drug interactions is low. Therefore, it seems that pitavastatin should preferentially be considered in the treatment of dyslipidemia in diabetic patients or at risk of developing diabetes.

Topics: Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Simvastatin is a statin used to lower low-density lipoprotein cholesterol, but has limitations in patients on complicated regimens due to concerns about drug-drug interactions. Pitavastatin is a newly developed statin with limited drug-drug interactions. We conducted a meta-analysis to compare the clinical efficacy of simvastatin and pitavastatin in the control of hypercholesterolemia.. Randomized clinical trials comparing the efficacy of pitavastatin and simvastatin were identified by searching PubMed (2000-2014) and EMBASE (2000-2014). The primary outcome subjected to meta-analysis was percent change in low-density lipoprotein cholesterol compared with baseline.. Four clinical trials were selected for meta-analysis. A total of 908 patients treated with pitavastatin (2 or 4 mg/day) and 381 patients treated with simvastatin (20 or 40 mg/day) were included in the final statistical analysis. No statistically significant difference was identified between treatment with pitavastatin 4 mg/day and treatment with simvastatin 40 mg/day for 12 weeks (mean difference -0.66; 95% confidence interval -2.92, 1.61; P=0.57). Similarly, no statistically significant difference was observed between pitavastatin 2 mg/day and simvastatin 20 mg/day for 4 weeks (mean difference -2.19; 95% confidence interval -0.11, 4.49; P=0.06). Treatment with pitavastatin was noninferior to simvastatin in all of the secondary outcomes and the safety profile was similar between the two statins.. Pitavastatin is noninferior to simvastatin in lowering low-density lipoprotein cholesterol.

Topics: Adolescent; Adult; Aged; Humans; Hypercholesterolemia; Middle Aged; Quinolines; Randomized Controlled Trials as Topic; Simvastatin; Treatment Outcome; Young Adult

With the practice-shifting changes made with the most recent guidelines for treating blood cholesterol, more older patients may be prescribed statin therapy. Therefore, it is imperative that practitioners have not only a working knowledge of information related to statins, but more specifically to their efficacy and safety in elderly populations. Pitavastatin is the most recent statin to receive regulatory approval. It is indicated for the treatment of primary hyperlipidemia or mixed dyslipidemia as an adjunctive therapy to diet. The overall body of evidence for the efficacy and safety of pitavastatin in elderly patients is small. The available data suggest that the ability of pitavastatin to lower low-density lipoprotein cholesterol in elderly patients is at least similar, and may be greater than that seen in comparatively younger cohorts. Taken together, the limited available data suggest that pitavastatin is effective at improving lipid parameters in elderly patients with a similar safety profile to other agents in the class. Until data become available distinguishing pitavastatin from the other available options, its ultimate role in the hyperlipidemia treatment armamentarium remains unclear.

Topics: Aged; Cholesterol, LDL; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Patient Satisfaction; Quality of Life; Quinolines; Risk Assessment

Statins are the cornerstone of lipid-lowering therapy to reduce the risk of coronary heart disease. Rosuvastatin and pitavastatin are the two recently developed statins with less potential for drug interaction resulting in improved safety profiles.. This review summarizes the pharmacokinetics and drug interactions of rosuvastatin and pitavastatin. The materials reviewed were identified by searching PubMed for publications using 'rosuvastatin', 'pitavastatin', 'statins', 'pharmacokinetics' and 'drug interaction' as the search terms.. Rosuvastatin and pitavastatin have favorable pharmacokinetic and safety profiles as their disposition does not depend on or is only marginally influenced by cytochrome P450 (CYP) enzymes, thus potentially reducing the risk of drug-drug interactions of these two statins with other drugs known to inhibit CYP enzymes. However, drug transporters play a significant role in the disposition of rosuvastatin and pitavastatin and drug interactions may occur through these. Genetic polymorphisms in drug transporters may also affect the pharmacokinetics, drug interactions and/or the lipid-lowering effect of these statins to a different extent.

Topics: Animals; Cytochrome P-450 Enzyme System; Drug Evaluation, Preclinical; Drug Interactions; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Models, Animal; Pyrimidines; Quinolines; Rosuvastatin Calcium; Sulfonamides

Pitavastatin is the latest statin to be approved and has shown beneficial effects on plasma lipid profiles. The aim of the present meta-analysis was to assess both the efficacy and safety of pitavastatin versus simvastatin, one of the most commonly used statins.. A search of the MEDLINE, EMBASE, OVID and Cochrane Central Register of Controlled Trials (CENTRAL) databases was undertaken. Clinical trials evaluating the efficacy and safety of simvastatin versus pitavastatin, published up to February 2014, were identified. Trials were included if they (1) were randomized controlled trials (RCTs) of at least 12 weeks' duration; (2) included patients with primary hypercholesterolaemia or mixed dyslipidaemia; (3) studied outcomes included low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C); and (4) were published in the English language. A fixed-effects model was used for data analysis if no significant heterogeneity was present; otherwise a random-effects model was used. Efficacy is reflected by the mean difference in the percentage change of plasma lipid profiles. Treatment-emergent adverse events (TEAEs) are presented as risk ratio (RR).. A total of 1,468 patients were included in the meta-analysis. The results indicated similar efficacy of pitavastatin (versus simvastatin) in lowering LDL-C. Pitavastatin also had similar effects to simvastatin on other major aspects of plasma lipids, including TC, TG and HDL-C. Somewhat in contrast to common belief (based on distinct metabolism by P450 subtypes), the two statins did not differ in the incidence of TEAE.. In clinical trials, pitavastatin was comparable to simvastatin in both efficacy and safety profile. Large-scale, high-quality observational studies are required to determine whether the advantage of pitavastatin in metabolism profiles could be translated into noticeable benefits.

Topics: Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Randomized Controlled Trials as Topic; Simvastatin; Treatment Outcome

Pitavastatin is the last marketed statin. Different studies have shown that pitavastatin is more potent than pravastatin and simvastatin in reducing LDL-cholesterol levels, and equivalent to atorvastatin and rosuvastatin. Moreover, pitavastatin provides a significant and sustained increase of HDL-cholesterol levels. Remarkably, as pitavastatin is minimally metabolized by CYP, the risk of interactions with other drugs is low. Additionally, pitavastatin does not interfere with glucose metabolism in diabetics and non-diabetics, and exerts a beneficial effect in patients with renal dysfunction. However, although available information may suggest that pitavastatin can improve cardiovascular prognosis, data coming from specifically designed clinical trials are still warranted. The aim of this review was to update the available evidence about efficacy and safety of pitavastatin, and to analyze the place of pitavastatin in the current armamentarium for the treatment of patients with hypercholesterolemia.

Topics: Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed therapeutic class of drugs worldwide, with established clinical benefits both in terms of improving serum lipid profiles and reducing cardiovascular events and mortality. Although statins have a favorable risk-to-benefit ratio, they have the potential to cause adverse events which can result in muscular inflammation (myositis), muscle breakdown (rhabdomyolysis) and, ultimately, kidney failure. While the incidence of rhabdomyolysis is approximately 3.4 cases per 100,000 person-years with standard-dose statin therapy, the risk of developing the condition increases substantially at higher therapeutic doses. This effect may be exacerbated by prescribing statins in combination with certain other medications because drug � drug interactions increase statin exposure by interacting with enzymes that would normally be involved in their metabolism and clearance. Co-administration of drugs that inhibit the cytochrome P450 (CYP) enzymes responsible for metabolizing statins, or that interact with the organic anion-transporting polypeptides (OATPs) responsible for statin uptake into hepatocytes, substantially increases the risk of developing myotoxicity. Such effects vary among statins according to their metabolic profile. For example, pitavastatin, a novel statin approved for the treatment of hypercholesterolemia and combined (mixed) dyslipidemia, is not catabolized by CYP3A4, unlike other lipophilic statins, and may be less dependent on the OATP1B1 transporter for its uptake into hepatocytes before clearance. Such differences in drug � drug interaction profiles among available statins offer the possibility of reducing the risk of myotoxicity among high-risk patients.

Topics: Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Quinolines; Rhabdomyolysis; Risk

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are established first line treatments for hypercholesterolaemia. In addition to the direct effects of statins in reducing concentrations of atherogenic low density lipoprotein cholesterol (LDL-C), several studies have indicated that the beneficial effects of statins may be due to some of their cholesterol-independent, multiple (pleiotropic) effects which may differ between different members of the class. Pitavastatin is a novel synthetic lipophilic statin that has a number of pharmacodynamic and pharmacokinetic properties distinct from those of other statins, which may underlie its potential pleiotropic benefits in reducing cardiovascular risk factors. This review examines the principal pleiotropic effects of pitavastatin on endothelial function, vascular inflammation, oxidative stress and thrombosis. The article is based on a systematic literature search carried out in December 2010, together with more recent relevant publications where appropriate. The available data from clinical trials and in vitro and animal studies suggest that pitavastatin is not only effective in reducing LDL-C and triglycerides, but also has a range of other effects. These include increasing high density lipoprotein cholesterol, decreasing markers of platelet activation, improving cardiac, renal and endothelial function, and reducing endothelial stress, lipoprotein oxidation and, ultimately, improving the signs and symptoms of atherosclerosis. It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction.

Topics: Animals; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Models, Cardiovascular; Quinolines; Risk Factors; Triglycerides

Statins are currently the most effective drugs for lowering low-density lipoprotein cholesterol (LDL-C) and represent the first choice for treating hypercholesterolemia. Pitavastatin was launched as a new statin on the Japanese market in 2003, followed by Korea, Thailand, China, the United States and Europe. This review summarizes and evaluates new insights into pitavastatin, from clinical trials since 2010.. This article reviews studies that compare pitavastatin with various other statins: i) Randomized Head-to-Head Comparison of Pitavastatin, Atorvastatin, and Rosuvastatin for Safety and Efficacy (Quantity and Quality of LDL): the PATROL Trial; ii) various Phase III clinical trials in Western countries; iii) The Comparison of Preventive Effect on Cardiovascular Events With Different Statins (CIRCLE) study; and iv) The Livalo Effectiveness and Safety (LIVES) Study Extension. Pitavastatin was found to have a similar LDL-C-lowering effect to other strong statins but also had a strong HDL-C-elevating effect and did not worsen glucose metabolism.. Pitavastatin has been launched in various countries around the world as a statin with potent LDL-C-lowering activity that is virtually unmetabolized by the cytochrome P450 family, with relatively few drug-drug interactions and no adverse effects on blood glucose. Pitavastatin thus appears well suited to long-term use.

Topics: Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase III as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Randomized Controlled Trials as Topic

Pitavastatin (Livazo®, Livalo®), an inhibitor of HMG-CoA reductase (statin), is indicated for the reduction of elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, in adult patients with primary hypercholesterolaemia and mixed dyslipidaemia, when response to diet and other non-pharmacological measures is inadequate. Pitavastatin has a favourable pharmacological profile following oral administration, including its long half-life (up to 12 hours), selective uptake into hepatocytes and minimal metabolism by cytochrome P450 (CYP) enzymes. This latter property decreases the likelihood of drug-drug interactions with agents that are metabolized by, inhibit or induce CYP enzymes. Pitavastatin improved the lipid profile (including LDL-C, TC and high-density lipoprotein cholesterol levels) in patients with hypercholesterolaemia and mixed dyslipidaemia, according to large, pivotal phase III studies of up to 60 weeks' duration. In these trials, pitavastatin for 12 weeks was noninferior to simvastatin and atorvastatin in terms of the improvement from baseline in LDL-C levels. In similarly designed trials, pitavastatin improved lipid profiles and was noninferior to simvastatin in patients with high cardiovascular risk and demonstrated significantly greater LDL-C reduction than pravastatin in elderly patients. Furthermore, in patients with type 2 diabetes mellitus, although noninferiority criteria for the comparison with atorvastatin were not met in terms of the improvement from baseline in LDL-C levels, pitavastatin was associated with some improvements in the lipid profile. Pitavastatin also demonstrated substantial lipid-modifying effects in exclusively Asian populations in well designed clinical trials. Pitavastatin was generally well tolerated in clinical trials of up to 60 weeks' duration, with a tolerability profile generally similar to that of atorvastatin and simvastatin. Therefore, pitavastatin appears to be an attractive alternative for the treatment of patients with primary hyperlipidaemia or mixed dyslipidaemia who have not responded adequately to diet and other non-pharmacological measures, and may present a useful treatment option in patients requiring polypharmacy, such as those at high risk of cardiovascular disease. Further studies evaluating the effects of pitavastatin on clinical endpoints, such as cardiovascular morbidity and mortality, are required to confirm the longer-term benefits of pitavastatin.

Topics: Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Randomized Controlled Trials as Topic; Treatment Outcome

The Livalo Effectiveness and Safety (LIVES) study was an observational study to examine the efficacy and safety of pitavastatin, a newly developed drug, in approximately 20,000 Japanese patients with hypercholesterolemia. During a 2-year follow-up period, no significant problems concerning safety were observed upon treatment with pitavastatin. Pitavastatin demonstrated potent and stable lowering of the LDL-cholesterol level. The LIVES study subanalyses revealed significant and continuous elevation of HDL-cholesterol in association with pitavastatin treatment and also showed that the drug did not adversely affect glycemic control as evaluated by the glycohemoglobin A(1c) level. Moreover, pitavastatin treatment was associated with an increase in estimated glomerular filtration rate in subjects with chronic kidney disease. These results suggest the usefulness of pitavastatin in hypercholesterolemic patients from various backgrounds. The ongoing LIVES study extension is expected to provide further data on cardiovascular outcome in subjects treated with pitavastatin.

Topics: Aged; Cholesterol, HDL; Cholesterol, LDL; Diabetes Complications; Female; Follow-Up Studies; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Quinolines; Renal Insufficiency

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, have revolutionized the treatment of hypercholesterolemia and coronary artery disease prevention. However, there are considerable issues regarding statin safety and further development of residual risk control, particularly for diabetic and metabolic syndrome patients. Pitavastatin is a potent statin with low-density lipoprotein (LDL) cholesterol-lowering effects comparable to those of atorvastatin or rosuvastatin. Pitavastatin has a high-density lipoprotein (HDL) cholesterol raising effect, may improve insulin resistance, and has little influence on glucose metabolism. Considering these factors along with its unique pharmacokinetic properties, which suggest minimal drug-drug interaction, pitavastatin could provide an alternative treatment choice, especially in patients with glucose intolerance or diabetes mellitus. Many clinical trials are now underway to test the clinical efficacy of pitavastatin in various settings and are expected to provide further information.

Topics: Animals; Coronary Artery Disease; Diabetes Mellitus; Drug Interactions; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Quinolines

Compared to other statins, pitavastatin is a highly potent 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor and an efficient hepatocyte low-density lipoprotein-cholesterol (LDL-C) receptor inducer. Its characteristic structure (heptenoate as the basic structure, a core quinoline ring and side chains that include fluorophenyl and cyclopropyl moieties) provides improved pharmacokinetics and significant LDL-C-lowering efficacy at low doses. Unlike other statins, the cyclopropyl group on the pitavastatin molecule appears to divert the drug away from metabolism by cytochrome P450 (CYP) 3 A4 and allows only a small degree of clinically insignificant metabolism by CYP2C9. As a result, pitavastatin is minimally metabolized; most of the bioavailable fraction of an oral dose is excreted unchanged in the bile and is reabsorbed by the small intestine ready for enterohepatic recirculation. This process probably accounts for pitavastatin's increased bioavailability relative to most other statins and contributes to its prolonged duration of action. In addition to its potent LDL-C-lowering efficacy, a number of pleiotropic benefits that might lead to a reduction in residual risk have been suggested in vitro. These include beneficial effects on endothelial function, stabilisation of the coronary plaque, anti-inflammatory effects and anti-oxidation. With regard to the clinical safety and efficacy of pitavastatin, the Phase IV Collaborative study of Hypercholesterolemia drug Intervention and their Benefits for Atherosclerosis prevention (CHIBA study) showed similar changes in lipid profile with pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia. However, a subgroup analysis of the CHIBA study showed that pitavastatin produced more significant changes from baseline in LDL-C, TG, and HDL-C in patients with hypercholesterolemia and metabolic syndrome. The clinical usefulness of pitavastatin has been further demonstrated in a number of Japanese patient groups with hypercholesterolemia, including those with insulin resistance, low levels of high-density lipoprotein-cholesterol (HDL-C), high levels of C-reactive protein, and chronic kidney disease. Finally, the Japan Assessment of Pitavastatin and AtorvastatiN in Acute Coronary Syndrome (JAPAN-ACS) study showed that pitavastatin induces plaque regression in patients with ACS, which suggests potential benefits for pitavastatin in reducing CV risk.

Topics: Antioxidants; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase IV as Topic; Endothelium, Vascular; Hepatocytes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation; Japan; Metabolic Syndrome; Molecular Structure; Multicenter Studies as Topic; Plaque, Atherosclerotic; Pyrroles; Quinolines; Receptors, LDL

To review pitavastatin, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and determine its place in the treatment of hypercholesterolemia.. Literature was accessed through PubMed (1948-December 2009). Pitavastatin, itavastatin, nisvastatin, NK 104, and NKS 104 were used as search terms. Results were limited to articles written in the English language.. All articles identified from the data source were reviewed for inclusion. Articles included were those pertaining to the pharmacology and pharmacokinetic properties of pitavastatin, in addition to original research evaluating the clinical efficacy of pitavastatin for hypercholesterolemia.. Pitavastatin is an oral HMG-CoA reductase inhibitor recently approved by the Food and Drug Administration for the treatment of primary hyperlipidemia and mixed dyslipidemia. Pitavastatin 2 mg has been shown to be noninferior to atorvastatin 10 mg and simvastatin 20 mg with respect to low-density lipoprotein cholesterol (LDL-C)-lowering ability. Additionally, pitavastatin 2 mg was shown in one study to lower LDL-C significantly more than pravastatin 10 mg. As with other HMG-CoA reductase inhibitors, primary safety concerns are related to myopathies and alterations in liver enzyme levels. While efficacy regarding beneficial effects on lipid parameters is comparable to that of other agents, a potential advantage of pitavastatin is its cytochrome P450 (CYP450) independent elimination, thereby reducing the likelihood of clinically significant drug-drug interactions. However, this is not a unique property, as pravastatin and rosuvastatin also possess this property.. In light of the lack of outcome data, pitavastatin offers no clear advantage over other drugs in this class.

Topics: Cholesterol, LDL; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Randomized Controlled Trials as Topic

Many clinical trials of pitavastatin have been done since its launch. New insights on pitavastatin from these trials are summarized and evaluated.. The results of clinical studies using pitavastatin, from 2008 to 2009, the LIVES study, the JAPAN-ACS study, the CHIBA study, the PIAT study and Phase III clinical trials in the West are reviewed.. In the LIVES study, pitavastatin showed significant and continuous elevation of high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), as well as potential decrease in low-density lipoprotein cholesterol (LDL-C), in addition to long-term safety. Non-inferiority of pitavastatin against atorvastatin in the percentage change in plaque volume was proved in the JAPAN-ACS study. Also, comparable effects on LDL-C reduction rate of pitavastatin versus atorvastatin were confirmed in the CHIBA study and Phase III clinical trials in the West, and a greater increase in HDL-C was observed than with atorvastatin in the PIAT study.. Pitavastatin is a useful potent stain in raising HDL-C as well as in lowering of LDL-C, though a large-scale, clinical trial to confirm prevention of cardiovascular events is needed in the future.

Topics: Animals; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Glomerular Filtration Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Practice Guidelines as Topic; Pyrroles; Quinolines

Treatment for hypercholesterolemia aims to suppress the progression of early atherosclerotic changes and prevent the onset of future cardiovascular events. Drugs to treat hypercholesterolemia should thus have sufficient longterm lipid-lowering and direct antiatherosclerotic effects. Pitavastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) that was developed in Japan. In addition to its long-term lipid-lowering effects, pitavastatin also exerts pleiotropic effects against atherosclerotic changes. Although few studies have investigated the mechanism of pitavastatin, its pleiotropic effects have encouraged its use to treat both hypercholesterolemia and atherosclerosis. Pentraxin-related protein PTX3, a prototype protein of the pentraxin family, could serve as a novel useful blood marker to assess dynamic inflammation during the early atherosclerotic stages. This review clarifies the long-term lipid-lowering and antiatherosclerotic effects of pitavastatin.

Topics: Animals; Atherosclerosis; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Quinolines

Pitavastatin was first developed in Japan and is expanding the regions in which it is clinically available. A considerable number of clinical studies have been conducted and published to date on the usefulness of pitavastatin for patients with primary hypercholesterolemia or combined dyslipidemia. Pitavastatin demonstrates potent low-density lipoprotein cholesterol reduction at low doses of 1-4 mg/day. It also affects the regression of coronary plaques, as observed in intravascular ultrasound-guided percutaneous coronary intervention studies. Moreover, the persistent, long-term high-density lipoprotein cholesterol elevation observed in the populations treated with pitavastatin is worthy of further attention. The reported improvements in lipid profiles are consistent among the studies conducted in Japan, Korea, Thailand, and Europe. In light of accumulating clinical experience worldwide, pitavastatin is now expected to establish its position for preventing and treating cardiovascular disease.

Topics: Anticholesteremic Agents; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase III as Topic; Dyslipidemias; Heptanoic Acids; Humans; Hypercholesterolemia; Pyrroles; Quinolines; Randomized Controlled Trials as Topic; Treatment Outcome

The pitavastatin Phase III and IV studies assessed the efficacy and safety of standard dose pitavastatin vs. comparable doses of alternative statins in a broad range of patients with hypercholesterolaemia. Phase III studies conducted in Europe included five 12-week, randomised, double-blind trials evaluating the non-inferiority of pitavastatin 1-4mg vs. atorvastatin 10-20mg, simvastatin 20-40 mg and/or pravastatin 10-40mg in patients with primary hypercholesterolaemia and combined dyslipidaemia, including patients with high cardiovascular risk, type II diabetes, and age ≥65 years. The primary endpoint was the adjusted mean percent change from baseline in low-density lipoprotein-cholesterol (LDL-C); secondary endpoints included changes from baseline in lipid and lipoprotein profiles, LDL-C-target attainment rates and safety parameters. For each study, treatment was continued in open-label, long-term extension studies. Phase IV Japanese studies included CHIBA - a 12-week, open-label active control, non-inferiority investigator-led trial comparing the efficacy and safety of pitavastatin 2mg and atorvastatin 10 mg in patients with hypercholesterolaemia; PIAT - a 52-week open-label, investigator-led, randomised, parallel-group study comparing the efficacy and tolerability of pitavastatin 2mg and atorvastatin 10 mg in patients with hypercholesterolaemia and glucose intolerance; and LIVES - a 2-year prospective post-marketing surveillance of pitavastatin in 20,279 patients with hypercholesterolaemia. The primary endpoint for the first two studies was the percent change from baseline in non-high-density lipoprotein-C (non-HDL-C) and HDL-C, respectively; secondary endpoints included % changes from baseline in other lipid/lipoprotein parameters, safety and tolerability. Overall, Phase III and IV studies demonstrate that pitavastatin 1-4mg is well tolerated, improves atherogenic lipid profile and increases LDL-C target attainment rates with a similar or greater efficacy to comparable doses of atorvastatin, simvastatin and pravastatin in most patient groups. In each of these studies, improvements in lipid profile were sustained or improved during the long term suggesting benefits for continued treatment with pitavastatin.

Topics: Atorvastatin; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Dyslipidemias; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pravastatin; Pyrroles; Quinolines; Simvastatin

Managing dyslipidaemia is central to the management of cardiovascular disease. Most statins can reduce the 5-year incidence of major vascular events by 20%. In Europe, however, up to 53% of statin-treated patients fail to attain their low-density lipoprotein-cholesterol (LDL-C) target and residual risk remains high, even when targets are reached. Reasons for this include under-treatment due to insufficient starting doses/failure to uptitrate; poor persistence with therapy due to adverse events (AEs) or drug-drug interactions (DDIs); and failure to treat non-LDL-C risk factors, such as high triglycerides (TGs) and low high-density lipoprotein-C (HDL-C). Phase III and IV studies demonstrate that pitavastatin 1-4 mg has a similar or greater lipid-lowering efficacy to atorvastatin 10-20 mg, simvastatin 20-40 mg and pravastatin 10-40 mg, and is well-tolerated with a low incidence of adverse events (AEs). The SmPC recommends a usual starting dose of 1 mg, with dose-escalation if required. However, since the lower doses (1-2 mg) bring the majority of people with hypercholesterolaemia or combined dyslipidaemia to LDL-C target, the need for pitavastatin uptitration and the risk of under-treatment is low. In addition to reducing LDL-C, pitavastatin has a sustained beneficial effect on other atherogenic lipids, including TGs and HDL-C. Recent studies reveal that pitavastatin reduces coronary atheroma plaque volume as efficiently as atorvastatin and can improve the composition of coronary plaques, effects that are likely to reduce the risk of CV endpoints in patients with acute coronary syndrome. Moreover, pitavastatin has a number of pleiotropic effects that can reduce inflammation and lipid oxidation, improve endothelial function, reduce the metabolic changes associated with adiposity, and improve glucose metabolism and renal function. Compared to other statins, pitavastatin has a unique metabolic profile that could reduce the risk of DDIs, thereby providing a clear benefit in patients receiving polypharmacy. Overall, pitavastatin is a well tolerated and effective treatment for patients with hypercholesterolaemia and combined dyslipidaemia, especially in those with low HDL-C, and it should help improve LDL-C-target attainment rates by reducing the risk of under-treatment, minimising AE rates, and reducing the risk of DDIs in people requiring polypharmacy. Future and ongoing studies will directly compare the effects of pitavastatin vs. other statins on hard clinical

Topics: Animals; Clinical Trials as Topic; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Pitavastatin, (+)-monocalcium bis(3R,5S,6E)-7-(2-cyclopropyl-4-[4-fluorophenyl]-3-quinolyl-3,5-dihydroxy-6-heptenoate), is a totally synthetic statin developed in Japan with a molecular weight of 880.98. Pitavastatin achieves its potent pharmacologic action by strongly binding and inhibiting the active site of 3-hydroxy-3-methyl-glutaryl-CoA reductase, and has potent low-density lipoprotein-cholesterol-lowering effects similar to atorvastatin and rosuvastatin. One other characteristic of the agent is that pitavastatin is minimally metabolized by the cytochrome P450 isozymes; it undergoes glucuronidation and is converted to the inactive lactone form, and, therefore, the incidence of any drug interactions is reduced. Due to the promising results observed in clinical trials, it has the potential to be an excellent addition to the worldwide lipid management market.

Topics: Animals; Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Quinolines

The growing number of trials that have highlighted the benefit of intensive lowering of total- and low density lipoprotein (LDL)-cholesterol levels especially with statins has created a need for more efficacious agents. Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin; although, head-to-head studies are yet to be conducted.

Topics: Animals; Anticholesteremic Agents; Clinical Trials as Topic; Food-Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Liver; Quinolines; Treatment Outcome

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, has been shown to reduce major cardiovascular events in both primary and secondary prevention, and statins became one of the most widely prescribed classes of drugs throughout the world. Previously, statins have been well tolerated and have shown favorable safety profiles. However, the voluntary withdrawal of cerivastatin from the market because of a disproportionate number of reports of rhabdomyolysis-associated deaths drew attention to the pharmacokinetic profile of statins, which may possibly have been related to serious drug-drug interactions. Pitavastatin (NK-104, previously called itavastatin or nisvastatin, Kowa Company Ltd., Tokyo) is a novel, fully synthetic statin, which has a potent cholesterol-lowering action. The short-term and long-term lipid-modifying effects of pitavastatin have already been investigated in subjects with primary hypercholesterolemia, heterozygous familial hypercholesterolemia, hypertriglyceridemia, and type-2 diabetes mellitus accompanied by hyperlipidemia. Within the range of daily doses from 1 to 4 mg, the efficacy of pitavastatin as a lipid-lowering drug seems to be similar, or potentially superior, to that of atorvastatin. According to the results of pharmacokinetic studies, pitavastatin showed favorable and promising safety profile; it was only slightly metabolized by the cytochrome P450 (CYP) system, its lactone form had no inhibitory effects on the CYP3A4-mediated metabolism of concomitantly administered drugs; P-glycoprotein-mediated transport did not play a major role in its disposition, and pitavastatin did not inhibit P-glycoprotein activity. It could be concluded that pitavastatin could provide a new and potentially better therapeutic choice for lipid-modifying therapy than do the currently available statins. The efficacy and safety of higher dose treatment, as well as its long-term effects in the prevention of coronary artery disease, should be further investigated.

Topics: Animals; Arteriosclerosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipoproteins; Quinolines

Rosuvastatin (ZD4522) and pitavastatin (NK-104) are novel HMG-CoA reductase inhibitors with a peculiar pharmacological profile. In particular, they show a high potency in decreasing LDL-C and their catabolism is not mediated by the cytochrome P-450 3A4, thus reducing the potential for drug-drug interaction and improving the management of blood cholesterol. As the magnitude of LDL-C reduction is directly associated with the decrease in the incidence of myocardial infarction and mortality for CAD, statins with increased LDL-C lowering potency may ensure the achievement of target LDL-C levels and offer a more aggressive cholesterol control, further improving CAD morbidity and mortality.

Topics: Animals; Cholesterol, LDL; Clinical Trials as Topic; Coronary Disease; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Naphthalenes; Pyrimidines; Quinolines; Rosuvastatin Calcium; Sulfonamides

An elevated level of low-density lipoprotein (LDL)-cholesterol has been recognised as the most important risk factor for coronary artery disease (CAD). Development of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) ('statins'), a rate-limiting key enzyme of cholesterol synthesis pathway, has revolutionised the cholesterol-lowering therapy. In the last decade, effective primary and secondary preventive measures have been established in several statin trials to prevent future events of CAD by lowering LDL-cholesterol levels. These results supported the 'lower is better' hypothesis in the relationship between LDL-cholesterol levels and CAD. NK-104 (pitavastatin, previously named as itavastatin or nisvastatin, Kowa Company Ltd., Tokyo) has recently been developed as a new chemically synthesised and powerful statin. On the basis of reported data, the potency of NK-104 is dose-dependent and appears to be equivalent to that of atorvastatin. This new statin is safe and well-tolerated in the treatment of patients with hypercholesterolaemia. The cytochrome P450 system only slightly modifies NK-104, which suggests the clinical advantage of this agent, because the prevalence of clinically significant interactions with a number of other commonly used drugs can be considered to be extremely low. NK-104 can provide a new and potentially superior therapeutic agent when compared with currently available other statins. Randomised controlled clinical trials to assess the long-term effects of this new statin on CAD would be required.

Topics: Animals; Arteriosclerosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipid Metabolism; Lipids; Quinolines; Randomized Controlled Trials as Topic

This study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia.. This was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study.. A total of 388 patients were randomly assigned to the 1PC111 (n = 128), pitavastatin (n = 132), or ezetimibe (n = 128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (-50.50% [14.9%]) compared with either the pitavastatin (-36.11% [11.4%]; P < 0.001) or ezetimibe (-19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non-HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups.. 1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients.. gov identifier: NCT04643093.

Topics: Aged; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Humans; Hypercholesterolemia

Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia.. Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients.. The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups.. Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy.. gov identifier: NCT04584736.

Topics: Anticholesteremic Agents; Cholesterol, LDL; Double-Blind Method; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Treatment Outcome

There has been no report about outcome of pitavastatin versus atorvastatin therapy in high-risk patients with hypercholesterolemia.. Hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases (n = 664, age = 65, male = 54%, diabetes = 76%, primary prevention = 74%) were randomized to receive pitavastatin 2 mg/day (n = 332) or atorvastatin 10 mg/day (n = 332). Follow-up period was 240 weeks. The primary end point was a composite of cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. The secondary end point was a composite of the primary end point plus clinically indicated coronary revascularization for stable angina.. The mean low-density lipoprotein cholesterol (LDL-C) level at baseline was 149 mg/dL. The mean LDL-C levels at 1 year were 95 mg/dL in the pitavastatin group and 94 mg/dL in the atorvastatin group. There were no differences in LDL-C levels between both groups, however, pitavastatin significantly reduced the risk of the primary end point, compared to atorvastatin (pitavastatin = 2.9% and atorvastatin = 8.1%, HR, 0.366; 95% CI 0.170-0.787; P = 0.01 by multivariate Cox regression) as well as the risk of the secondary end point (pitavastatin = 4.5% and atorvastatin = 12.9%, HR = 0.350; 95%CI = 0.189-0.645, P = 0.001). The results for the primary and secondary end points were consistent across several prespecified subgroups. There were no differences in incidence of adverse events between the statins.. Pitavastatin therapy compared with atorvastatin more may prevent cardiovascular events in hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases despite similar effects on LDL-C levels.

Topics: Aged; Atorvastatin; Cardiovascular Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Pyrroles; Quinolines; Treatment Outcome

Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33-2.15), 1.61 (1.25-1.98), 1.61 (1.01-2.21), and 1.68 (1.19-2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.

Topics: Aged; Atorvastatin; Cholesterol, LDL; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Plaque, Atherosclerotic; Quinolines; Taiwan

Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG).. In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA. The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Cholesterol; Fasting; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Lipids; Male; Middle Aged; Quinolines

Statins decrease cholesteryl ester transfer protein (CETP) levels, which have been positively associated with hepatic lipid content as well as serum low density lipoproteins-cholesterol (LDL-C) levels. However, the relationship between the CETP status and statin-induced reductions in LDL-C levels has not yet been elucidated in detail. We herein examined the influence of the CETP status on the lipid-reducing effects of pitavastatin in hypercholesterolemic patients with type 2 diabetes mellitus as well as the molecular mechanism underlying pitavastatin-induced modifications in CETP levels.. Fifty-three patients were treated with 2 mg of pitavastatin for 3 months. Serum levels of LDL-C, small dense (sd) LDL-C, and CETP were measured before and after the pitavastatin treatment. The effects of pitavastatin, T0901317, a specific agonist for liver X receptor (LXR) that reflects hepatic cholesterol contents, and LXR silencing on CETP mRNA expression in HepG2 cells were also examined by a real-time PCR assay.. The pitavastatin treatment decreased LDL-C, sdLDL-C, and CETP levels by 39, 42, and 23%, respectively. Despite the absence of a significant association between CETP and LDL-C levels at baseline, baseline CETP levels and its percentage change were an independent positive determinant for the changes observed in LDL-C and sdLDL-C levels. The LXR activation with T0901317 (0.5 μM), an in vitro condition analogous to hepatic cholesterol accumulation, increased CETP mRNA levels in HepG2 cells by approximately 220%, while LXR silencing markedly diminished the increased expression of CETP. Pitavastatin (5 μM) decreased basal CETP mRNA levels by 21%, and this was completely reversed by T0901317.. Baseline CETP levels may predict the lipid-reducing effects of pitavastatin. Pitavastatin-induced CETP reductions may be partially attributed to decreased LXR activity, predictable by the ensuing decline in hepatic cholesterol synthesis.. UMIN Clinical Trials Registry ID UMIN000019020.

Topics: Aged; Cholesterol Ester Transfer Proteins; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Hep G2 Cells; Humans; Hydrocarbons, Fluorinated; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Liver X Receptors; Male; Middle Aged; Quinolines; Sulfonamides; Treatment Outcome

This study aimed to clarify the relationships between arterial remodeling patterns and plaque volume regression or stabilization. The TOGETHAR trial is a prospective open-label trial designed to assess coronary plaque regression and stabilization with multiple plaque imaging modalities following 52 weeks of pitavastatin treatment (2 mg/day). Coronary plaques were observed in 46 patients with both angioscopy and intravascular ultrasound at baseline and after 52 weeks of drug treatment. We divided these patients into three groups according to their remodeling indices (RI). Group P consisted of patients with a baseline RI >1.05, Group M of patients with a baseline RI of 0.95-1.05, and Group N of patients with a baseline RI <0.95 and then evaluated differences in coronary plaque volume changes and yellow grade among the three groups. In the positive remodeling group, whose remodeling index (RI) exceeded 1.05 at baseline, RI and percent atheroma volume (PAV) were significantly reduced (RI 1.14 ± 0.07 to 1.05 ± 0.10, p = 0.010, PAV 47.3 ± 8.3 to 45.3 ± 7.3 mm(3), p = 0.048). There was no relationship between baseline RI and the change in yellow grade of plaque. RI increased without significant change of PAV or a decrease in lumen volume in group N, with RI below 0.95 at baseline. Plaques with positive remodeling were more likely to have plaque volume regression by pitavastatin than those without in patients with coronary artery disease. Moreover, plaques with positive and negative remodeling were changed into those with intermediate remodeling by pitavastatin. Pitavastatin might induce not only plaque regression or stabilization, but also conformational normalization of vessel structure.

Topics: Aged; Angioscopy; Coronary Artery Disease; Coronary Vessels; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Quinolines; Remission Induction; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Remodeling

Recently, investigation may have focused on modification of apolipoprotein A-I (apoA-I) associated with anti-inflammatory effect for the potential prevention of cardiovascular events. The purpose of this study was to evaluate the effects of atorvastatin and pitavastatin on serum apoA-I levels and to investigate the role of apoA-I in the anti-inflammatory effect of statin. We conducted a 6-month, prospective, randomized, open-label study in which we assigned hypercholesterolemic patients to a pitavastatin group (n = 52; 2 mg/day) or an atorvastatin group (n = 52; 10 mg/day) to investigate the effects of these two statins on the serum apoA-I levels and serum high-sensitivity C-reactive protein (hs-CRP) levels. There were no significant differences between the two groups in the changes in the low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), or hs-CRP levels, but the change in apoA-I in the pitavastatin group was significantly greater than in the atorvastatin group (5.3 vs. 1.4 %; p = 0.0001). A stepwise regression analysis revealed that the percent change in (Δ) serum apoA-I level was an independent predictor of the Δ serum hs-CRP (standard correlation coefficient = -0.198; p = 0.047). However, there was a significant negative correlation between the Δ apoA-I levels and Δ hs-CRP levels in the pitavastatin group (r = -0.283, p = 0.042), but not the atorvastatin group (r = -0.133, p = 0.356). The results suggest that the contribution of apoA-I to the reduction in serum hs-CRP levels by these two statins may be different. A decrease in hs-CRP level accompanied by an increase in apoA-I level may be involved in the pleiotropic effects of pitavastatin.

Topics: Aged; Anticholesteremic Agents; Apolipoprotein A-I; Atorvastatin; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Prospective Studies; Quinolines; Regression Analysis

Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia (HC) is unknown.. To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and arterial stiffness (β), three surrogate markers of atherosclerosis were studied in HC patients.. A randomized, double-blind trial was performed with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks. There were 20 patients in each group, and 30 gender- and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated by β were measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on all subjects.. At baseline, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced FMD, and increased β and IMT were observed in HC patients (P<0.001 for all) compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL-C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups had reduced β and improved endothelial function over the 8-week follow-up (P<0.05-0.001); nonetheless, no significant alterations of IMT were found (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05-0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and β (P<0.001-0.000) were found.. Treatment with pitavastatin calcium exerted favorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.

Topics: Aged; Atherosclerosis; Body Mass Index; Brachial Artery; Calcium; Carotid Arteries; Carotid Intima-Media Thickness; Cholesterol, LDL; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Quinolines; Vascular Stiffness; Vasodilation

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear.. A total of 146 patients with hypercholesterolemia without known cardiovascular disease were randomly assigned to receive 5 mg/day of atorvastatin (n=73) or 1 mg/day of pitavastatin (n=73).. At baseline, age, gender, blood pressure, lipid profiles, and the serum monocyte chemoattractant protein (MCP)-1, homeostasis model assessment of insulin resistance (HOMA-IR) and CIMT values were comparable between the groups. After 12 months of treatment, atorvastatin and pitavastatin equally reduced the LDL cholesterol levels; however, atorvastatin increased the HOMA-IR by ＋26% and pitavastatin decreased this parameter by －13% (p＜0.001). The MCP-1 values were reduced by －28% in the patients treated with pitavastatin and only －11% in those treated with atorvastatin (p=0.016). A greater percent decrease in the mean CIMT from baseline was observed in the patients treated with pitavastatin than in those treated with atorvastatin (－4.9% vs. －0.5%, p=0.020).. These data indicate that, while these agents significantly and equally reduce the LDL cholesterol levels, atorvastatin and pitavastatin have different effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis in patients with dyslipidemia.

Topics: Aged; Atorvastatin; Carotid Artery Diseases; Carotid Intima-Media Thickness; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation; Insulin Resistance; Male; Prognosis; Prospective Studies; Quinolines

Circulating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some high-dose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs.This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting.. A pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients.. A total of 26 patients (19 with T2DM) completed the study. While the lipid-lowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs.. While both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins.. This trial is registered at ClinicalTrials.gov, NCT01386853.

Topics: Aged; Atorvastatin; Biomarkers; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelial Progenitor Cells; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pilot Projects; Prospective Studies; Pyrroles; Quinolines; Risk Factors; Treatment Outcome; Vascular Endothelial Growth Factor A

Although there have been several reports that statins cause insulin resistance that leads to the occurrence of type 2 diabetes in Caucasians, there has been no Japanese prospective studies investigating the effects of statins on the glucose metabolism system.. Our subjects were 86 Japanese patients with type 2 diabetes with hypercholesterolemia. Pitavastatin 2mg/day was administered for 12 months and the lipid-related values, glucose metabolism values, and the presence/absence of side effects were investigated.. None of these factors was found to differ between before and after administration of pitavastatin in overall analysis of all subjects. In subgroup analysis, fasting blood glucose showed a decrease in the BMI ≥ 25 group and there was a significant difference between the BMI<25 and BMI ≥2 5 groups (P-values: 0.021 and 0.0036). Although HbA1c showed an increase both in the group switched to pitavastatin and the BMI<25 group (P-values: 0.035 and 0.033) and HOMA-β showed a decrease in the BMI<25 group (P-values: 0.044), there were no significant differences in changes between each divided group and their counterparts.. In the Japanese obese group with BMI ≥ 25, pitavastatin elicited a significant decrease in fasting blood glucose. It is not clear whether or not this is due to improved insulin resistance as a direct effect of pitavastatin, but in contrast to findings in Caucasians pitavastatin does not worsen insulin resistance in Japanese patients with type 2 diabetes complicated by hypercholesterolemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Prospective Studies; Quinolines; Treatment Outcome

Many large-scale clinical trials have confirmed that statins are effective in reducing low-density lipoprotein cholesterol (LDL-C) level, resulting in reducing cardiovascular events. Recent studies have focused on the effects of statins on high-density lipoprotein cholesterol (HDL-C). Here we compared the effects of two statins on lipid profile and other metabolic parameters.. The study population included 129 patients with stable coronary artery disease, hypercholesterolemia, and hypo-HDL-cholesterolemia (HDL-C<50mg/dl). They were randomly allocated to treatment by pitavastatin 2-4 mg/day or atorvastatin 10-20mg/day and followed-up for 30 months. The primary endpoint was percent changes in HDL-C and adiponectin during the study. The secondary endpoints were percent and absolute changes in markers of glucose metabolism, serum lipids, and apolipoproteins.. The effects of 30-month treatment with pitavastatin on HDL-C were significantly greater than those of atorvastatin (%change: pitavastatin: 20.1 ± 25.7%, atorvastatin: 6.3 ± 19.8%, p=0.01; absolute change: pitavastatin: 7.3 ± 9.1mg/dl, atorvastatin: 2.3 ± 8.0mg/dl, p=0.02). A similar trend was seen with regard to apolipoprotein-AI (ApoAI) (%change: pitavastatin: 20.8 ± 19.3%, atorvastatin: 11.4 ± 17.6%, p=0.03; absolute change: pitavastatin: 23.1 ± 20.2mg/dl, atorvastatin: 12.1 ± 19.4 mg/dl, p=0.02). Treatment with pitavastatin, but not atorvastatin, significantly increased adiponectin levels. Neither statin had a significant effect on hemoglobin A1c. No severe adverse events were registered during the study.. Long-term treatment with pitavastatin resulted in significantly greater increases in serum HDL-C and ApoAI levels without adverse effects on glucose metabolism, compared with atorvastatin.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Apolipoprotein A-I; Atorvastatin; Cholesterol, HDL; Coronary Artery Disease; Endpoint Determination; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Pyrroles; Quinolines; Young Adult

Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.. Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = -35.0 ± 14.1% and atorvastatin group = -38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (-37.1 ± 12.9% vs. -38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.. Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.. ClinicalTrials.gov NCT01386853 http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Lipoproteins; Male; Middle Aged; Pyrroles; Quinolines; Risk Factors; Treatment Outcome; Triglycerides

To assess the long-term efficacy, safety and tolerability of pitavastatin (2 and 4 mg) in elderly patients (≥ 65 years of age) with primary hypercholesterolaemia or combined (mixed) dyslipidaemia.. Patients (n = 545) who had completed a 12-week double-blind comparative study (core study) of pitavastatin and pravastatin entered a 60-week, open-label, multicentre extension study of pitavastatin. The initial daily dose was 2 mg, increasing to 4 mg after 8 weeks if necessary to achieve treatment targets. The proportion of patients attaining European Atherosclerosis Society (EAS) and National Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) targets for low-density lipoprotein cholesterol (LDL-C) was determined.. Of the patients enrolled, 539 received at least one dose of pitavastatin (safety population: men, 45.5%; Caucasian, 99.1%; mean age, 70.3 years; range, 65-89 years). Only 17% of patients required up-titration to pitavastatin 4 mg. After 60 weeks, NCEP ATP III and EAS targets were attained by 93.8% and 89.0% of patients, respectively. Plasma LDL-C declined by 43.4% and high-density lipoprotein cholesterol increased by 9.6% versus core-study baseline values. Pitavastatin was well tolerated: the most common treatment-emergent adverse events were nasopharyngitis, mild/moderate myalgia and hypertension. There were no cases of severe myalgia, myopathy, myositis or rhabdomyolysis, and no significant findings on urinalysis, vital signs or 12-lead ECG.. Long-term pitavastatin treatment (2 and 4 mg) is effective in lowering LDL-C levels and has a good safety and tolerability profile in elderly patients.

Topics: Aged; Aged, 80 and over; Cholesterol, LDL; Drug Tolerance; Dyslipidemias; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Quinolines; Treatment Outcome

To compare the safety and efficacy of once-daily pitavastatin (1, 2, and 4 mg) and pravastatin (10, 20, and 40 mg) in elderly patients (≥ 65 years of age) with primary hypercholesterolaemia or combined (mixed) dyslipidaemia.. After a 6-8-week washout/dietary period, patients were randomized to six treatment groups (1, 2, or 4 mg pitavastatin vs. 10, 20, or 40 mg pravastatin) in a 12-week multicentre double-blind study. Patients (n = 942; men, 44.3%; Caucasian, 99.3%; mean age, 70 years; age range, 65-89 years) in all groups were well matched for duration of disease and diagnosis.. Mean decreases in low-density lipoprotein cholesterol over 12 weeks were 31.4-44.3% with pitavastatin 1-4 mg and 22.4-34.0% with pravastatin 10-40 mg (p < 0.001 for all dose comparisons). Compared with pravastatin, pitavastatin provided greater decreases in total cholesterol and apolipoprotein B in all dose groups (p < 0.001) and triglycerides in the low-dose (p = 0.001) and higher-dose (p = 0.016) groups, and greater increases in high-density lipoprotein cholesterol in the intermediate-dose (p = 0.013) and higher-dose (p = 0.023) groups. The proportions of patients achieving the European Atherosclerosis Society target with pitavastatin and pravastatin, respectively, were: low doses, 59.9 and 37.9%; intermediate doses, 79.5 and 51.0%; higher doses, 88.1 and 65.7% (p < 0.001 for all comparisons). Both statins were well tolerated, with no reports of myopathy or rhabdomyolysis.. Pitavastatin provides superior efficacy and comparable tolerability to pravastatin in elderly patients.

Topics: Aged; Aged, 80 and over; Cholesterol, LDL; Double-Blind Method; Drug Tolerance; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Pravastatin; Quinolines; Time Factors; Treatment Outcome

The effects of potent statins on oxidized lipoprotein biomarkers are not well defined.. The VISION (Value of oxIdant lipid lowering effect by Statin InterventiON in hypercholesterolemia) Trial randomized patients with hypercholesterolemia to 12-week administration of pitavastatin 2 mg/day (n = 21) or atorvastatin 10 mg/day (n = 21) and a variety of lipoprotein oxidative biomarkers were measured. Between-group analysis did not reveal any differences except in the ratio of malondialdehyde (MDA)-LDL over apolipoprotein B-100 (MDA-LDL/apoB) in pitavastatin vs. atorvastatin group (-13% vs. -0.7%, p = 0.04). Within-group changes from baseline to 12-week revealed significant increases in OxPL/apoB and reductions in small-dense LDL, MDA-LDL, and lipoprotein-associated phospholipase A(2) measured on circulating apoB particles (Lp-PLA(2)/apoB) in both groups and significant reductions in OxPL/apoAI in the atorvastatin group.. The VISION study describes the first comparison on lipoprotein oxidation biomarkers between pitavastatin and atorvastatin and suggests diverse effects on lipoprotein oxidation markers in patients with hypercholesterolemia.

Topics: Atorvastatin; Biomarkers; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Oxidation-Reduction; Prospective Studies; Pyrroles; Quinolines

This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease (NAFLD) with hypercholesterolemia.. Serum samples of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated. Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC-MS)/MS. These data were then compared with those of 36 sex- and age-matched healthy controls. In addition, changes in these markers produced by treatment with pitavastatin were evaluated.. Serum non-cholesterol sterols, reflecting intestinal cholesterol absorption, were significantly lower in the NAFLD patients compared to the controls, and the cholesterol synthesis marker, the ratio of lathosterol to cholesterol, was not significantly different between the two groups. Serum proportions of liver X receptor α (LXRα) ligand oxysterols (ratios to cholesterol) were significantly elevated in the NAFLD patients compared to the controls. The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance (HOMA-IR) were significantly correlated. The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment, from 3 months after initiation of the treatment, and the suppression remained significant during the observation period. The markers representing cholesterol absorption were unchanged at 3 months, but had significantly increased at 12 months. Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment.. We speculate that serum LXRα ligand oxysterol levels (relative to cholesterol) could be surrogate markers of insulin resistance, and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD.

Topics: Adult; Biomarkers; Case-Control Studies; Cholesterol; Chromatography, Liquid; Fatty Liver; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Lipid Metabolism; Liver X Receptors; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Orphan Nuclear Receptors; Prospective Studies; Quinolines; Tandem Mass Spectrometry; Young Adult

To evaluate the safety and efficacy of pitavastatin in patients with hypercholesterolemia in China under conditions of extensive usage.. This was a 12-week, multicenter, open-label, without parallel-group comparison, phase IV clinical trial.. There were 427 subjects in the safety set. The adverse events mainly included vomiting, myalgia and the elevations of aspartate transaminase (AST), alanine transaminase (ALT) and creatine kinase (CK), etc. The incidence of drug-related adverse events was 4.22%. There were no significant differences between pre-exposure and post-exposure average levels of renal function indicators and blood routine examination item (all P > 0.05). None of them had a high AST/ALT value, i.e. > 3 times upper limits of normal (ULN), or had a high CK value, i.e. > 10 times ULN. There were 397 subjects in the per protocol set. At week 12 post-treatment, the blood levels of total cholesterol and low density lipoprotein cholesterol (LDL-C) in subjects without previous treatment decreased 24.6% and 31.0% respectively, that of high density lipoprotein cholesterol (HDL-C) in subjects with HDL-C < 1.04 mmol/L increased 60.1% while that of triglyceride (TG) in subjects with TG > 1.70 mmol/L decreased 22.5% (P < 0.05). And 207 (92.3%) subjects were at a low risk, 46 (76.1%) subjects at an intermediate risk, 134 (47.8%) subjects at a high risk and 10 (40.0%) of subjects at a very high risk had achieved a LDL-C target value; the LDL-C goal achievement rate after switching from previous medication to pitavastatin was significant higher than that of pre-switching.. Pitavastatin demonstrates positive safety and efficacy. It may be used for the treatment of patients with hypercholesterolemia in China.

Topics: Aged; Anticholesteremic Agents; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Quinolines

Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted.. To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial.. This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks.. In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009).. Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Topics: Adiponectin; Atherosclerosis; C-Reactive Protein; Cholesterol, HDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation; Metabolic Syndrome; Molecular Weight; Oxidative Stress; Quinolines; Time Factors

To evaluate the effect of pitavastatin on blood glucose in patients with hypercholesterolemia, and to investigate the efficacy of pitavastatin in diabetic patients combined with hypercholesterolemia.. This study was a 12-week, multi-center, open-label, without parallel-group comparison, phase IV clinical trail.. Contrasting to baseline, the prevalences at week 4 and 12 post-treatment of abnormal fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) (FPG: 14.2%vs 14.1% and 11.0%; HbA1c: 14.3% vs 15.1% and 16.1%) in the safety set subjects without diabetes mellitus (DM), as well as in those with DM but not taking glucose-lowering drugs (FPG: 7/7 vs 4/7 and 5/7; HbA1c: 5/5 vs 4/4 and 5/5) had no significant changes (all P values > 0.05). Contrasting to baseline, the levels of TC [(6.51 ± 0.94) mmol/L vs (5.12 ± 0.93) mmol/L and (4.54 ± 1.00) mmol/L], LDL-C [(4.11 ± 0.79) mmol/L vs (3.02 ± 0.81) mmol/L and (2.51 ± 0.70) mmol/L] and TG [2.10 (1.53, 2.54) mmol/L vs 1.62 (1.26, 2.00) mmol/L and 1.35 (1.10, 1.86) mmol/L]at week 4 and 12 post-treatment in the per protocol set 55 subjects with DM were significantly reduced (all P values < 0.05); 33.3% of subjects at high risk and 10.0% of subjects at very high risk had achieved a TC target value; 55.6% of subjects at high risk and 40.0% of subjects at very high risk had achieved a LDL-C target value.. Pitavastatin has a safe effect on blood glucose and it could be used to treat diabetic patients combined with hypercholesterolemia in China.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Quinolines

To evaluate the effect of pitavastatin on high sensitivity C-reactive protein (hsCRP) in patients with hypercholesterolemia, and determine risk factors for the effect.. This study was a 12-week, multicenter, open-label, without parallel-group comparison, phase IV clinical trail.. There were 330 subjects in the per protocol set. Contrast to the baseline, the average levels of hsCRP in all of subjects and the group without a history of receiving previous statin medication at week 12 post-treatment decreased respectively 26.4% (1.20 mg/L vs 1.68 mg/L) and 27.5% (1.21 mg/L vs 1.97 mg/L, all P < 0.05). The results of multilevel models indicated that the average levels of hsCRP reduced with the passage of treatment time, the time-varying rate of per-visit was 0.97 mg/L (95% confidence interval 0.96 - 0.98). Controlled individual background covariates, the model predicted that pulse pressure and white blood cell count on the baseline had the significant positive effects on hsCRP (P < 0.01).. Pitavastatin decreases hsCRP in patients with hypercholesterolemia. The main risk factors for the effect are pulse pressure and white blood cell count on the baseline.

Topics: Adult; Aged; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Quinolines; Risk Factors

Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study.. The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured.. TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r = 0.259, p = 0.0181); however, percent changes in these levels were not significantly correlated.. Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects.

Topics: Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Interleukin-18; Japan; Male; Middle Aged; Prospective Studies; Quinolines

Effects of pitavastatin and atorvastatin on the lipid profile and lipoprotein subclasses were compared in patients with Type 2 diabetes with dyslipidaemia.. Patients with Type 2 diabetes with hypercholesterolaemia and/or hypertriglyceridaemia were randomized to receive pitavastatin 2 mg (n = 16) or atorvastatin 10 mg (n = 15) for 6 months, and blood lipid and lipoprotein profiles and cholesterol and triglyceride contents of 20 lipoprotein subclasses, determined by high-performance liquid chromatography, were compared.. At baseline, cholesterol in VLDL and LDL subclasses were increased equally in two groups of patients with diabetes as compared with normolipidaemic control subjects. As compared with baseline, serum levels of total cholesterol, LDL cholesterol, non-HDL cholesterol, LDL cholesterol:HDL cholesterol ratio and apolipoprotein B were decreased after 1, 3 and 6 months of treatment with atorvastatin and pitavastatin. Serum triglyceride levels were decreased after 1, 3 and 6 months of atorvastatin, but only at 3 months of pitavastatin. Serum HDL cholesterol was increased after 1, 3 and 6 months of pitavastatin, whereas HDL cholesterol was even decreased after 6 months of atorvastatin. Cholesterol levels of most VLDL and LDL subclasses were decreased equally in both groups. However, only pitavastatin increased cholesterol of medium HDL subclass. Serum triglyceride and triglyceride contents in VLDL and LDL subclasses were decreased only by atorvastatin.. The impact on lipoprotein subclass profiles was different between pitavastatin and atorvastatin. It may be beneficial to determine lipoprotein subclass profile and select the appropriate statin for each profile in patients with diabetes with an additional cardiovascular risk such as low HDL cholesterol or hypertriglyceridaemia.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Pyrroles; Quinolines; Treatment Outcome

Atorvastatin, rosuvastatin and pitavastatin are available for intensive, aggressive low-density lipoprotein cholesterol (LDL-C)-lowering therapy in clinical practice. The objective of the Randomized Head-to-Head Comparison of Pitavastatin, Atorvastatin, and Rosuvastatin for Safety and Efficacy (Quantity and Quality of LDL) (PATROL) Trial was to compare the safety and efficacy of atorvastatin, rosuvastatin and pitavastatin head to head in patients with hypercholesterolemia. This is the first prospective randomized multi-center trial to compare these strong statins (UMIN Registration No: 000000586).. Patients with risk factors for coronary artery disease and elevated LDL-C levels were randomized to receive atorvastatin (10mg/day), rosuvastatin (2.5mg/day), or pitavastatin (2mg/day) for 16 weeks. Safety was assessed in terms of adverse event rates, including abnormal clinical laboratory variables related to liver and kidney function and skeletal muscle. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Three hundred and two patients (from 51 centers) were enrolled, and these 3 strong statins equally reduced LDL-C and LDL particles, as well as fast-migrating LDL (modified LDL) by 40-45%. Newly developed pitavastatin was non-inferior to the other 2 statins in lowering LDL-C. There were no differences in the rate of adverse drug reactions among the 3 groups, but HbA(1c) was increased while uric acid was decreased in the atorvastatin and rosuvastatin groups.. The safety and efficacy of these 3 strong statins are equal. It is suggested that the use of these 3 statins be completely dependent on physician discretion based on patient background.

Topics: Aged; Analysis of Variance; Atorvastatin; Biomarkers; Cholesterol, LDL; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Patient Selection; Prospective Studies; Pyrimidines; Pyrroles; Quinolines; Rosuvastatin Calcium; Sulfonamides; Time Factors; Treatment Outcome

The Livalo Effectiveness and Safety (LIVES) study was an observational study to examine the efficacy and safety of pitavastatin, a newly developed drug, in approximately 20,000 Japanese patients with hypercholesterolemia. During a 2-year follow-up period, no significant problems concerning safety were observed upon treatment with pitavastatin. Pitavastatin demonstrated potent and stable lowering of the LDL-cholesterol level. The LIVES study subanalyses revealed significant and continuous elevation of HDL-cholesterol in association with pitavastatin treatment and also showed that the drug did not adversely affect glycemic control as evaluated by the glycohemoglobin A(1c) level. Moreover, pitavastatin treatment was associated with an increase in estimated glomerular filtration rate in subjects with chronic kidney disease. These results suggest the usefulness of pitavastatin in hypercholesterolemic patients from various backgrounds. The ongoing LIVES study extension is expected to provide further data on cardiovascular outcome in subjects treated with pitavastatin.

Topics: Aged; Cholesterol, HDL; Cholesterol, LDL; Diabetes Complications; Female; Follow-Up Studies; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Quinolines; Renal Insufficiency

To investigate whether endothelial function can be improved by the treatment of pitavastatin calcium via its antioxidant properties in hypercholesteremia patients.. Forty patients with hypercholesteremia were randomized to receive pitavastatin calcium 1 or 2 mg/day for 8 weeks. Among them, four people were lost in the follow-up period. Before and after treatment, clinical and biochemical characteristics, markers of oxidative stress (plasma 8-iso-prostaglandin F(2α) and serum gp91phox) were determined and concomitantly endothelium-dependent brachial artery flow-mediated dilation (FMD) was measured by ultrasound examination. Thirty healthy subjects were chosen as controls.. For individuals with hypercholesteremia, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and serum gp91phox were significantly increased (p<0.001 for all) and plasma 8-iso-prostaglandinF2α (8-iso-PGF2α) was significantly higher (p<0.05), while FMD was obviously impaired (p<0.001). Total cholesterol, LDL-C and serum gp91phox were significantly reduced (p<0.001 for all), plasma 8-iso-PGF2α was lower and FMD was significantly improved after pitavastatin calcium treatment compared with those before treatment in any group (p<0.05 for both). However, there was no significant difference between the 1-mg and 2-mg pitavastatin calcium groups post-therapy.. Endothelial dysfunction induced by hypercholesteremia can be ameliorated by pitavastatin calcium treatment, which occurs in part through its antioxidative properties.

Topics: Antioxidants; Brachial Artery; Case-Control Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Oxidative Stress; Quinolines; Ultrasonography

Topics: Atorvastatin; Cholesterol, LDL; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pyrimidines; Pyrroles; Quinolines; Rosuvastatin Calcium; Sulfonamides

Although a low level of high density lipoprotein-cholesterol (HDL-C) is an important risk factor for coronary heart disease, few available agents are capable of significantly increasing HDL-C. This multicenter study demonstrated that administration of pitavastatin, a new HMG-CoA reductase inhibitor, significantly and persistently increased HDL-C (from 36.0+/-5.9 to 40.5+/-9.1 mg/dL: p<0.001) and apolipoprotein A-I levels (from 108.4+/-18.0 to 118.7+/-19.3 mg/dL: p<0.01) in 43 hypercholesterolemic patients with low HDL-C over the course of 12 months of treatment. This suggests that pitavastatin may contribute to reduction in coronary heart disease.

Topics: Aged; Apolipoprotein A-I; Cholesterol, HDL; Coronary Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Quinolines

In addition to their cholesterol-lowering effect, statins increase high-density lipoprotein cholesterol (HDL-C) levels. Endothelial lipase (EL) is a regulator of plasma HDL-C levels. In the present study, the effects of statins on EL expression were investigated.. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin suppressed basal and cytokine-treated EL expression in endothelial cells. Concomitant treatment with mevalonate or geranylgeranyl pyrophosphate completely reversed the inhibitory effect of pitavastatin, suggesting that geranylgeranylated proteins are involved in the inhibition of EL expression by statins. Inhibition of RhoA activity by overexpression of a dominant-negative mutant of RhoA or a Rho kinase inhibitor decreased EL levels. Pitavastatin reduced phospholipase activities of endothelial cells, and concomitant treatment with mevalonate reversed its inhibitory effect. Pitavastatin reduced RhoA activity and EL expression in mouse tissues. Furthermore, plasma EL concentrations in human subjects were measured by enzyme-linked immunosorbent assays. Plasma EL levels were negatively associated with plasma HDL levels in 237 patients with cardiovascular diseases, and pitavastatin treatment reduced plasma EL levels and increased HDL-C levels in 48 patients with hypercholesterolaemia.. These findings suggest that statins can reduce EL expression in vitro and in vivo via inhibition of RhoA activity. The inhibition of EL expression in the vessel wall may contribute to the anti-atherogenic effects of statins.

Topics: Adult; Aged; Aged, 80 and over; Animals; Cells, Cultured; Cholesterol, HDL; Dose-Response Relationship, Drug; Down-Regulation; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipase; Male; Mevalonic Acid; Mice; Mice, Inbred C57BL; Middle Aged; Polyisoprenyl Phosphates; Prospective Studies; Protein Kinase Inhibitors; Protein Prenylation; Quinolines; rho-Associated Kinases; rhoA GTP-Binding Protein; Time Factors; Transfection; Treatment Outcome

Previous studies have shown conflicting results on low-density lipoprotein cholesterol (LDL-C) reduction for comparable doses of pitavastatin and atorvastatin.. To compare the efficacy of pitavastatin 1 mg once daily with that of atorvastatin 10 mg once daily on lipoprotein change, safety, and cost per percent LDL-C reduction.. An 8-week, randomized, open-label, parallel trial was conducted in patients with hypercholesterolemia. One hundred patients were equally randomized to receive pitavastatin 1 mg once daily or atorvastatin 10 mg once daily; 98 completed the study. Outcomes were assessed at baseline and at the end of the study.. Pitavastatin lowered LDL-C levels from baseline by 37% compared with 46% in the atorvastatin group (p < 0.001). The reduction of total cholesterol (TC) levels from baseline was significantly different between the pitavastatin (28%) and atorvastatin (32%) groups (p = 0.005). There was no significant difference in the percentage of changes in triglyceride and high-density lipoprotein cholesterol levels between groups. The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the pitavastatin (74%) and atorvastatin (84%) groups (p = 0.220). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times the upper normal limit of alanine aminotransferase or 10 times that of creatine kinase. The monthly cost per percent LDL-C reduction in the pitavastatin group ($0.77) was about 50% lower than the cost in the atorvastatin ($1.56) group.. Although pitavastatin 1 mg daily was not as effective at lowering LDL-C and TC levels as atorvastatin 10 mg daily, the number of patients achieving their LDL-C goals with pitavastatin was comparable with the number using atorvastatin. Pitavastatin 1 mg once daily may be an alternative regimen with cost-saving benefits but without a significant decrease in therapeutic benefit or increase in adverse events in patients with hypercholesterolemia.

Topics: Adult; Aged; Aged, 80 and over; Atorvastatin; Cholesterol; Cholesterol, LDL; Cost-Benefit Analysis; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Prospective Studies; Pyrroles; Quinolines; Treatment Outcome

The aim of this study was to determine the impact of pitavastatin on low-density lipoprotein cholesterol (LDL-C) and lectin-like oxidized LDL receptor-1 (LOX-1) in patients with hypercholesterolemia. Twenty-five hypercholesterolemic patients (8 male, 17 female; age 66 +/- 13, 21-80 years) who had not received anti-dyslipidemic agents and had LDL-C levels of more than 160 mg/dL were examined. Biochemical factors were measured at baseline and after treatment with pitavastatin (2 mg/day) for 6 months. Serum levels of LOX-1 with apolipoprotein B-100 particle ligand and a soluble form of LOX-1 (sLOX-1) were measured by ELISA. All subjects completed the study with no adverse side effects. Total-C (268 +/- 26 vs. 176 +/- 17 mg/dL), LDL-C (182 +/- 21 vs. 96 +/- 14 mg/dL), and LOX-1 ligand (867 +/- 452 vs. 435 +/- 262 ng/mL) were reduced with pitavastatin treatment (P < 0.0001 for each). Significant decreases in triacylglycerols were noted (P < 0.0001), but there were no changes in high-density lipoprotein cholesterol. After 6 months, there were no significant changes in high-sensitivity CRP or soluble LOX-1. At baseline, there were no significant correlations between LOX-1 ligand and either LDL-C or sLOX-1. The decrease in LOX-1 ligand was not correlated with the decrease in LDL-C, but was correlated with the decrease in sLOX-1 (r = 0.47, P < 0.05). In conclusion, pitavastatin therapy had beneficial effects on markers of oxidative stress in hypercholesterolemic subjects. Serum levels of LOX-1 ligand may be a useful biomarker of the pleiotropic effects of statins.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Biomarkers; Cholesterol, LDL; Down-Regulation; Female; Humans; Hypercholesterolemia; Ligands; Male; Middle Aged; Quinolines; Scavenger Receptors, Class E; Young Adult

Lipid-lowering therapy with a statin not only powerfully lowers cholesterol but also exerts anti-inflammatory effects by decreasing serum C-reactive protein (CRP). Since an angiotensin II, type-1 receptor antagonist (ARB) also decreases CRP levels, the add-on effect of statins on CRP may be worth exploring. We determined the effect of pitavastatin on serum levels of highly sensitive CRP (hs-CRP) in 30 patients with hypercholesterolemia undergoing treatment with anti-hypertensive medication including ARBs. Pitavastatin, 2 mg daily, was given. The control group consisted of hypertensive patients without hyperlipidemia. The low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hs-CRP were measured at baseline, 1, 3, 6, and 12 months after treatment. For the atherosclerotic index, LDL-C/HDL-C ratios at 12 months were calculated. The LDL-C level was markedly reduced at 1 month and thereafter. The baseline level of hs-CRP in the hyperlipidemia group was significantly higher than that in the control group (1.647 ± 0.210 mg/L vs. 0.666 ± 0.097 mg/L p < 0.0001). After 3 months, the percentage of reduction of hs-CRP was significantly higher than that in the control group. The absolute values of hs-CRP were significantly decreased to a level similar to the control group, and the hs-CRP in both groups was remained at the same level for 12 months. Although the LDL-C/HDL-C ratios of the pitavastatin group was significantly reduced from 3.3 to 1.8, those of the control group were not changed. In conclusion, pitavastatin was found to have powerful anti-inflammatory, add-on effects over the similar effects of ARB as assessed by hs-CRP.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; C-Reactive Protein; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Male; Middle Aged; Quinolines; Treatment Outcome

The effect of a strong, lipophilic statin (pitavastatin) on the thoracic aorta has not yet been elucidated. The purpose of the present study was to evaluate the effects of pitavastatin (P) therapy on plaque components and morphology in the thoracic aorta by transesophageal echocardiography (TEE) and clarify the impact of the therapy on media and intima in patients with hypercholesterolemia. Sixty-four media and 64 intima of the thoracic aorta were investigated in 32 patients with hypercholesterolemia. The corrected integrated backscatter (c-IBS) values in the thoracic aortic wall and intima-media thickness (IMT) at the same site were measured before and after P therapy or diet (D) for 7 mo. Moreover, c-IBS values in media were measured in 168 patients without hypercholesterolemia to estimate age-dependent changes. C-IBS values in media were correlated with age (r = 0.84, p < 0.001). C-IBS and IMT of media in the P group significantly decreased from -17.8 +/- 2.4 to -20.1 +/- 3.7 dB and from 1.7 +/- 0.3 to 1.5 +/- 0.3 mm, respectively (p < 0.001), whereas those in the D group significantly increased from -18.3 +/- 2.0 to -16.7 +/- 2.1 dB and from 1.6 +/- 0.3 to 1.7 +/- 0.2 mm, respectively (p < 0.001). IMT in intima in the P group significantly decreased from 3.7 +/- 0.4 to 3.3 +/- 0.4 mm (p < 0.001). C-IBS in intima in the P group significantly increased from -10.2 +/- 2.2 to -6.9 +/- 1.7 dB, which indicated plaque stabilization. Pitavastatin improved the atherosis measured by IMT and sclerosis measured by c-IBS values in the media and induced stabilization and regression of plaques in the intima of the thoracic aorta.

Topics: Aged; Aorta, Thoracic; Atherosclerosis; Atrial Fibrillation; Diet; Echocardiography, Transesophageal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Middle Aged; Observer Variation; Prospective Studies; Quinolines; Scattering, Radiation; Treatment Outcome; Tunica Intima; Tunica Media

Topics: Atherosclerosis; Atorvastatin; Diabetes Mellitus, Type 2; Glucose Intolerance; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pyrroles; Quinolines; Treatment Outcome

The primary objective of this study was to demonstrate equivalence of pitavastatin compared with simvastatin in the reduction of low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia or combined dyslipidaemia. Secondary objectives included achievement of National Cholesterol Education Program Adult Treatment Panel (NECP) and European Atherosclerosis Society (EAS) LDL-C goals, comparison of other lipid parameters, and assessment of safety and tolerability of the two statins.. A prospective, randomised, active-controlled double-blind, double-dummy, 12-week therapy trial was conducted in 857 patients with either primary hypercholesterolaemia or combined dyslipidaemia. The trial was designed to demonstrate the equivalence (non-inferiority of presumed equipotent doses) of pitavastatin compared with simvastatin. Patients were randomised to one of four groups: pitavastatin 2 mg/day, pitavastatin 4 mg/day, simvastatin 20 mg/day or simvastatin 40 mg/day. The main study limitation was restriction of the study population to those eligible for administration of simvastatin.. This clinical trial has been registered at www.clinicaltrials.gov NCT# NCT00309777.. Pitavastatin 2 mg showed significantly better reductions of LDL-C (p = 0.014), non-high-density lipoprotein cholesterol (non-HDL-C) (p = 0.021) and total cholesterol (TC) (p = 0.041) compared with simvastatin 20 mg and led to more patients achieving the EAS LDL-C treatment target. Reduction of LDL-C in the pitavastatin 2 mg group was 39% compared with 35% in the simvastatin 20 mg group. Pitavastatin 4 mg showed similar effects on all lipid parameters to simvastatin 40 mg. The reductions in LDL-C were 44% and 43%, respectively. The safety profiles of pitavastatin and simvastatin were similar at the two dose levels. Pitavastatin was considered superior to simvastatin in terms of percent reduction of LDL-C in the lower dose group comparison and proved to be equivalent to simvastatin in percent reduction of LDL-C in the higher-dose group.. As compared with simvastatin, an established first-line lipid-lowering agent, pitavastatin is an efficacious treatment choice in patients with primary hypercholesterolaemia or combined dyslipidaemia.

Topics: Adult; Aged; Biomarkers; Double-Blind Method; Dyslipidemias; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Quinolines; Simvastatin; Treatment Outcome

The effects of statin on small dense low-density lipoprotein cholesterol (sd-LDL-C) and remnant-like particle cholesterol (RLP-C) levels in heterozygous familial hypercholesterolemia (FH) have not been examined. This study aimed to clarify the effects of statin on sd-LDL-C and RLP-C levels in heterozygous FH.. Seventeen patients with heterozygous FH were randomly assigned to 2 mg/day pitavastatin or 10 mg/day atorvastatin. At baseline and 12 weeks after treatment with statin, we measured sd-LDL-C and RLP-C levels.. Sd-LDL-C levels significantly decreased from 43 +/- 24 to 16 +/- 10 mg/dL (-63%, p=0.001) in the pitavastatin group, and from 44 +/- 17 to 19 +/- 10 mg/dL (-55%, p<0.001) in the atorvastatin group. RLP-C levels decreased from 8.4 +/- 2.8 to 6.6 +/- 2.7 mg/dL (-16%, p=0.156) in the pitava-statin group, and from 9.8 +/- 4.7 to 5.9 +/- 5.4 mg/dL (-45%, p=0.044) in the atorvastatin group. There were no significant differences in percent changes of sd-LDL-C (p=0.370) and RLP-C levels (p=0.097) between the two groups.. Sd-LDL-C measured by the heparin-magnesium precipitation method and RLP-C levels in heterozygous FH were decreased by 12 weeks of statin therapy. Statin might have additional anti-atherogenic effects by reducing not only LDL-C but also sd-LDL-C and RLP-C.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Cholesterol, LDL; Female; Heptanoic Acids; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Models, Biological; Pyrroles; Quinolines; Regression Analysis; Triglycerides

Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared.. This study compared the effects of pitavastatin and atorvastatin on HDL-C and other lipids and glucose metabolism in Japanese patients with elevated LDL-C levels and glucose intolerance. The tolerability of the 2 treatments was also compared.. This was a multicenter, open-label, parallel-group trial. Patients with LDL-C levels>or=140 mg/dL and glucose intolerance (defined according to Japanese criteria for borderline diabetes and World Health Organization criteria for impaired fasting glucose and impaired glucose tolerance) were randomly assigned to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d for 52 weeks. Levels of serum lipids and lipoproteins and measures of glucose metabolism (fasting insulin, fasting glucose, glycosylated hemoglobin, and homeostasis model assessment for insulin resistance) were obtained at baseline and at 8, 26, and 52 weeks of treatment. The effect of study drug on glucose metabolism was evaluated as a tolerability outcome. Tolerability was further assessed based on adverse events, either spontaneously reported or elicited by questioning; physical examination findings; and clinical laboratory test results. Study physicians rated the relationship of adverse events to study medication as unrelated, suspected, or probable.. Two hundred seven patients were enrolled in the study, and efficacy was evaluated in 173 patients (88 pitavastatin, 85 atorvastatin). Thirty-four patients were excluded for reasons including failure to start medication or lack of >or=6 months of follow-up. Women accounted for 62% (108/173) of the evaluable population, which had a mean age of 63.3 years and a mean weight of 63.0 kg; 89% (154/173) had diabetes mellitus. The percent change in HDL-C levels was significantly greater in the pitavastatin group compared with the atorvastatin group (8.2 vs 2.9, respectively; P=0.031), as was the percent change in apolipoprotein (Apo) A-I (5.1 vs 0.6; P=0.019). The percent change in LDL-C levels was significantly lower with atorvastatin compared with pitavastatin (-40.1 vs -33.0, respectively; P=0.002), as were the percent changes in non-HDL-C (-37.4 vs -31.1; P=0.004), Apo B (-35.1 vs -28.2; P<0.001), and Apo E (-28.1 vs -17.8; P<0.001). The significant results for these parameters were unchanged when all 189 subjects who received>or=1 dose of study medication were included in the analysis, using last-value-carried-forward methodology. There were no significant differences between treatments with respect to the measures of glucose metabolism. Both statins appeared to be well tolerated. Adverse events occurred in 9% (9/96) of the pitavastatin group and 14% (13/93) of the atorvastatin group (P=NS). Two patients in the pitavastatin group and none in the atorvastatin group had an alanine aminotransferase value>3 times the upper limit of normal (P=NS).. In these patients with elevated LDL-C levels and glucose intolerance, 52 weeks of treatment with pitavastatin 2 mg/d was associated with significantly greater increases in HDL-C and Apo A-I levels than atorvastatin 10 mg/d. Both treatments were well tolerated.

Topics: Anticholesteremic Agents; Atorvastatin; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Enzyme Inhibitors; Female; Follow-Up Studies; Glucose Intolerance; Heptanoic Acids; Humans; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Japan; Male; Middle Aged; Pyrroles; Quinolines; Time Factors; Treatment Outcome

The effect of pitavastatin on high-sensitivity C-reactive protein (hs-CRP) has not been reported, yet, in humans. We, therefore, investigated the effects of pitavastatin on lipid profiles and hs-CRP in Japanese subjects with hypercholesterolemia.. The subjects were 178 Japanese with hypercholesterolemia, including 103 (58%) with type 2 diabetes. Pitavastatin (12 mg/day) was administered for 12 months. Serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG) and hs-CRP levels were measured for 12 months.. Serum LDL-C and RLP-C levels were significantly decreased by 30.3% and 22.8%, respectively. Serum TG levels were decreased by 15.9% in subjects with basal TG levels above 150 mg/dl. Serum HDL-C levels were significantly increased. The administration of pitavastatin reduced serum hs-CRP levels by 34.8%. No serious adverse events were observed, including changes in glycosylated hemoglobin levels of diabetic patients.. These results suggest that pitavastatin significantly improves lipid profiles and reduces proinflammatory responses, without adverse effects, in Japanese subjects with hypercholesterolemia, including those with diabetes mellitus.

Topics: Aged; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Enzyme Inhibitors; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Lipids; Male; Middle Aged; Prospective Studies; Quinolines; Triglycerides

We compared short- and intermediate-term effects on lipid profiles, fibrinolytic parameter, and endothelial function between pitavastatin and atorvastatin. Short-term improvement of endothelial function was superior with pitavastatin compared to atorvastatin therapy. Pitavastatin could be a potentially better therapeutic choice for lipid-lowering and early alterations in endothelial function. Our study provides an important basis on which further trials involving larger numbers of patients may be studied prospectively.

Topics: Aged; Atorvastatin; Coronary Artery Disease; Endothelium, Vascular; Female; Fibrinolysis; Heptanoic Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Prospective Studies; Pyrroles; Quinolines; Time Factors; Vasodilation

Hypercholesterolemia is a well-established risk factor for the development of vascular events. Statins have pleiotropic effects beyond reducing the low-density lipoprotein-cholesterol (LDL-C) concentration. This study sought to determine whether treatment with pitavastatin affects latent regional left ventricular (LV) systolic and diastolic dysfunction and carotid arterial stiffness in patients with hypercholesterolemia and preserved LV ejection fraction (LVEF), using newly developed ultrasonic strain imaging and carotid ultrasonography.. A total of 30 patients with hypercholesterolemia (>or=220 mg/dl for serum total cholesterol, and/or >or=140 mg/dl for LDL-C) were randomized to either administration of pitavastatin (1 or 2 mg/day; n=15) or no statin therapy (n=15) for 12 months. LV systolic and diastolic functions were evaluated by measuring transmitral flow velocity, mitral annular motion velocity, and the myocardial strain and strain rate profiles using pulsed Doppler, tissue velocity, and ultrasonic strain imaging. Subclinical atherosclerosis also was determined by measuring the intima - media thickness (IMT) and stiffness beta of the left and right common carotid arteries using B- and M-mode ultrasonography. During the follow-up period, the mean peak systolic strains of the LV posterior and inferior walls increased from 39.2+/-15.9% to 51.5+/-17.7% (p<0.01) and 46.0+/-12.2% to 57.5+/-10.3% (p<0.01), respectively, in the pitavastatin group compared with the no statin group. The mean peak early diastolic strain rates of the LV posterior and inferior walls also increased from -6.5+/-2.9 s(-1) to -9.5+/-2.8 s(-1) (p<0.01) and -6.5+/-2.5 s(-1) to -9.1+/-2.7 s(-1) (p<0.01), respectively, in the pitavastatin group. The stiffness beta decreased from 5.6+/-2.5 to 4.1+/-0.8 (p<0.05) in the pitavastatin group, whereas there was no significant change in IMT.. One year of pitavastatin treatment improved not only carotid arterial stiffness but also regional LV systolic and diastolic function in patients with hypercholesterolemia and preserved LVEF. Ultrasonic strain imaging has the potential to become a sensitive tool for detecting the effects of early medical intervention on latent regional LV myocardial dysfunction in this patient population.

Topics: Adult; Aged; Carotid Artery, Common; Echocardiography; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Quinolines; Stroke Volume; Tunica Intima; Vascular Resistance; Ventricular Function, Left

To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia.. Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated.. Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.

Topics: Aged; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Body Mass Index; Body Weight; Cholesterol, LDL; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Japan; Male; Middle Aged; Pyrroles; Quinolines; Waist Circumference

No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. We thus evaluated the effects of pitavastatin, which does not undergo first-pass metabolism, on bone metabolism.. According to the therapeutic regimen, the subjects were divided into two groups (group A, 66 with pitavastatin; group B, 35 without pitavastatin). Bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) as bone turnover markers (BTMs) were compared between the two groups and between at baseline and after 3 months of treatment in each group. Correlations between baseline characteristics and deltaBTMs, and between delta lipid profile and deltaBTMs were investigated using both Pearson's correlation analysis and multivariate analysis.. The subjects were 101 patients with untreated hypercholesterolemia.. After 3 months of treatment, BAP in group A did not change significantly compared with either the baseline value or that in group B. However, NTx in group A significantly decreased compared with both the baseline value and that in group B. In addition, deltaNTx was negatively correlated with NTx at baseline, and the significance of this correlation persisted after multiple regression analysis.. Our findings suggest that pitavastatin may have potentially beneficial effects on bone metabolism primarily by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

Topics: Adult; Aged; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Resorption; Collagen Type I; Enzyme Inhibitors; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Multivariate Analysis; Osteogenesis; Osteoporosis; Peptides; Prospective Studies; Quinolines; Time Factors

Although previous studies have examined the efficacy of pitavastatin, its tolerability and effects on lipid concentrations have not been compared with those of atorvastatin in a multicenter, randomized study.. This trial compared the efficacy and tolerability of pitavastatin and atorvastatin in hypercholesterolemic Korean adults.. This 8-week, multicenter, randomized, open-label, dose-titration study was conducted at 18 clinical centers in Korea between May 2005 and February 2006. After a 4-week dietary lead-in period, patients with hypercholesterolemia were randomized to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d. Patients who had not reached the low-density lipoprotein cholesterol (LDL-C) goal by week 4 received a double dose of the assigned medication for an additional 4 weeks. Efficacy was evaluated in terms of achievement of the National Cholesterol Education Program Adult Treatment Panel III LDL-C goals and changes from baseline in other lipids and high-sensitivity C-reactive protein (hs-CRP). The tolerability profile was assessed by physical and electro-cardiographic examinations, laboratory tests, and recording adverse reactions at all visits.. A total of 268 patients were randomized to treatment, and 222 (82.8%) completed the study (149 women, 73 men; mean age, 59 years; mean weight, 63.5 kg). At the end of the study, there was no significant difference between the pitavastatin and atorvastatin groups in the proportion of patients achieving the LDL-C goal (92.7% [102/110] vs 92.0% [103/112], respectively). In addition, there were no significant differences between groups in terms of the percent changes from baseline in LDL-C, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), or hs-CRP. Twenty-six of 136 patients (19.1%) taking pitavastatin reported 35 treatment-emergent adverse reactions; 33 of 132 patients (25.0%) taking atorvastatin reported 39 treatment-emergent adverse reactions. Elevations in creatine kinase were observed in 6 patients (4.4%) in the pitavastatin group and 7 patients (5.3%) in the atorvastatin group. There were no serious adverse drug reactions in either group.. In these adult Korean patients with hypercholesterolemia, pitavastatin and atorvastatin did not differ significantly in terms of the proportions of patients achieving the LDL-C goal; reductions in LDL-C, total cholesterol, and triglycerides; or increases in HDL-C. Both drugs were well tolerated.

Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Korea; Male; Middle Aged; Pyrroles; Quinolines; Triglycerides

Pitavastatin is a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor used to treat hypercholesterolemia.. The goal of this study was to compare the efficacy and safety of pitavastatin versus those of simvastatin in Korean patients with hypercholesterolemia.. This was an 8-week, multicenter, prospective, randomized, open-label, Phase III clinical trial. Male and female Korean patients with hypercholesterolemia who were between the ages of 20 and 75 years and who had a fasting triglyceride level <600 mg/dL and a low-density lipoprotein (LDL) cholesterol level >130 mg/dL after a 4-week dietary lead-in period were eligible for entry. Eligible patients were randomized into 2 groups in a 1:1 ratio. Patients received pitavastatin 2 mg once daily or simvastatin 20 mg once daily for 8 weeks. The medication was administered initially for 4 weeks, and an additional 4 weeks of study medication was prescribed at week 4. The final visit was conducted 8 weeks after randomization.. Of the 104 patients randomized to treatment, 95 patients (59 women; 36 men) completed the study (49 in the pitavastatin group [mean age, 59.9 years] and 46 in the simvastatin group [mean age, 56.4 years]). No significant difference was found between groups with respect to patient age, sex, or body mass index. There was no significant difference in the percent decrease in LDL cholesterol levels (mean [SD], 38.2% [11.6%] decrease for the pitavastatin group vs 39.4% [12.9%] decrease for the simvastatin group [P = 0.648]). Also, there were no significant differences between the 2 study groups in the percent changes in total cholesterol, triglyceride, or high-density lipoprotein (HDL) cholesterol levels from baseline to study end. No significant difference was observed for the proportion of patients who achieved the LDL cholesterol goal of the National Cholesterol Education Program Adult Treatment Panel III: 93.9% (46/49) of patients in the pitavastatin group and 91.3% (42/46) of patients in the simvastatin group (P = 0.709) met the target level. At least 1 clinical adverse event and at least 1 adverse drug reaction were observed in 25.0% (13/52) and 11.5% (6/52), respectively, of patients in the pitavastatin group, and 37.3% (19/51) and 23.5% (12/51), respectively, in the simvastatin group; this difference was not statistically significant. The most common adverse event was an elevation in creatine kinase levels >2 times the upper limit of normal in 3.8% of pitavastatin-treated patients and 9.8% of simvastatin-treated patients (P = 0.269). There were no serious adverse drug reactions observed in either group.. The HMG-CoA reductase inhibitor pitavastatin was found to be noninferior to simvastatin in terms of reducing LDL cholesterol, total cholesterol, and triglyceride levels, and increasing HDL cholesterol levels, in Korean patients with hypercholesterolemia after 8 weeks of treatment.

Topics: Adult; Aged; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Korea; Male; Middle Aged; Prospective Studies; Quinolines; Simvastatin

Pitavastatin (p-INN) is a novel and fully synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with a cholesterol-lowering action stronger than that of other statins currently in use. A 12-week, multi-center, randomized, double-blind, controlled study was conducted to confirm the efficacy and safety of pitavastatin compared with pravastatin, an agent for using to reduce low density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. Patients were recruited at 43 institutes in Japan. Following more than 4 weeks run-in period, 240 patients were randomized to receive 2 mg of pitavastatin or 10 mg of pravastatin daily. At 12 weeks post-randomization, the pitavastatin group showed significantly lower LDL-C levels by -37.6% from baseline compared with -18.4% in the pravastatin group (P<0.05). Pitavastatin also significantly lowered total cholesterol (TC) by -28.2% compared with -14.0% of pravastatin (P<0.05). The LDL-C target level of <140 mg/dl was attained in 75% of the patients treated with pitavastatin, compared with 36% of those in the pravastatin group (P<0.05). Pitavastatin also significantly reduced triglycerides (TG), apo B, C-II and C-III, compared with pravastatin, and increased HDL-C, apo A-I and A-II, to the same extent of pravastatin. Safety was assessed by monitoring adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. These results indicated that pitavastatin was more effective than pravastatin, and both drugs were well-tolerated in the treatment of hypercholesterolemia.

Topics: Adult; Aged; Cholesterol; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Quinolines; Safety

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Topics: Adult; Aged; Atorvastatin; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Primary Prevention; Pyrroles; Quinolines; Retrospective Studies; Rosuvastatin Calcium; Simvastatin

While randomized controlled trials provide useful information about drug safety and efficacy, they do not always reflect the observed results in the real world. The prospective, observational, non-comparative trial in South Korea was designed to evaluate the efficacy and safety of pitavastatin in clinical practice in 28,343 patients.. This study was conducted in 893 facilities in Korea from April 2, 2012 to April 1, 2017. This study was designed to administer 1, 2, or 4 mg pitavastatin to patients with hyperlipidemia at the age of 20 or older for at least 8 weeks.. For 126 days of mean duration of administration of pitavastatin, the % change of low density lipoprotein cholesterol indicated a dose dependent reduction: -23.4%, -29.1%, and -35.2% in the 1, 2, and 4 mg groups, respectively in patients who have not been treated with lipid lowering medications prior to study. Only 1.74% (492/28,343) of pitavastatin-treated patients experienced adverse events, of which 0.43% (123/28,343) were adverse drug reactions. Less than 1% of patients experienced the grade 2 or more toxicity (Common Terminology Criteria for Adverse Events v4.03) in alanine aminotransferase, aspartate aminotransferase, serum creatinine, and serum creatine phosphokinase. Although there were no rhabdomyolysis in 28,343 patients, 0.04% of patients had been reported pitavastatin-related musculoskeletal disorders.. Overall, this observational study showed that pitavastatin was well tolerated and effectively modified the lipid profile, reducing cardiovascular and cerebrovascular risk in Korean patients with hypercholesterolemia in the real world.

Topics: Adult; Aged; Aged, 80 and over; Cholesterol, LDL; Dose-Response Relationship, Drug; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Prospective Studies; Quinolines; Republic of Korea; Treatment Outcome; Young Adult

Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity.. This study was a prospective study including 48 statin-naïve patients (age, 58.2±8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β. Compared with baseline, there was significant improvement in circumferential CAS (2.98%±1.18% to 3.40%±1.43%, p=0.008) and β. Short-term treatment with high-dose pitavastatin improved carotid artery elasticity measured by speckle-tracking method, but not conventional parameters by B-mode ultrasound. Speckle-tracking-based measurements may allow the early noninvasive assessment of statin effects on vascular function in hypercholesterolemic patients.

Topics: Carotid Arteries; Carotid Intima-Media Thickness; Elasticity; Elasticity Imaging Techniques; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Prognosis; Prospective Studies; Quinolines

Topics: Cardiovascular Diseases; Cholesterol, HDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Epidemiological studies have shown that low HDL predicts cardiovascular risk just as much as elevated LDL cholesterol levels. However, today we know that HDL functionality is more important than HDL levels. As a group effect, statins increase HDL levels. They are also thought to increase functional HDL. Pitavastatin is a new statin with a different structure, shown to increase HDL levels more than other statins as well as functionality. Studies have shown that plaque regression occurs with pitavastatin. These findings provide the expectation that it will also decrease cardiovascular events.

Topics: Cardiovascular Diseases; Cholesterol, HDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Plaque, Atherosclerotic; Quinolines

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are used to control blood cholesterol levels and reduce cardiovascular disease. It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM). However, limited evidence exists from direct head to head comparisons of statins on whether the risk of DM differs among statins. We investigated the risk of development of new-onset diabetes in subjects treated with different statins.. We retrospectively enrolled consecutive 3680 patients without DM or impaired fasting glucose who started receiving statin treatment for cholesterol control. We evaluated the incidence of new-onset diabetes according to the type of statin.. The mean duration of follow-up was 62.6±15.3 months. The incidence of DM was significantly higher in the pitavastatin group (49 of 628; 7.8%) compared to that in the other statin groups [atorvastatin (68 of 1327; 5.1%), rosuvastatin (77 of 1191; 6.5%), simvastatin (11 of 326; 3.4%), and pravastatin (12 of 298; 5.8%); p=0.041]. The risk of diabetes was the highest in the pitavastatin group compared with that in the simvastatin group [hazard ratio (HR)=2.68, p=0.011]. Other statins showed no significant risk differences compared to that for simvastatin. Fasting blood glucose (FBG) level at baseline and body-mass index (BMI) were associated with the development of diabetes [FBG, HR=1.11, p<0.001; BMI, HR=1.02, p=0.005].. Among the five statins, pitavastatin showed the strongest effect on the development of new-onset diabetes.

Topics: Aged; Atorvastatin; Diabetes Mellitus; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Pyrimidines; Pyrroles; Quinolines; Retrospective Studies; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Topics: Atorvastatin; Drug Substitution; Electromyography; Fasciculation; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Leg; Middle Aged; Muscle Cramp; Phytosterols; Quinolines; Rosuvastatin Calcium; Toes

An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid impacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and lipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by single or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats.. Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13), ezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily, pitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each group respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were determined by ELISA and lipid profile were measured by enzymatic assay.. Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin plus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p < 0.05 compared with placebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy. Ezetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or co-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with regard to lipid profile levels at day 3 (P > 0.05).. Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly attenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination may be better than the latter in future clinical application.

Topics: Animals; Azetidines; Drug Combinations; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Proprotein Convertase 9; Quinolines; Rats; Rats, Sprague-Dawley; Serine Endopeptidases

Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity.. To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits.. Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%.. Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2.. Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

Topics: Animal Experimentation; Animals; Aorta, Thoracic; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Endothelium, Vascular; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipid Peroxidation; Male; Quinolines; Rabbits; Triglycerides

Topics: Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Leukocytes, Mononuclear; Ligands; Lipopolysaccharide Receptors; Male; Matrix Metalloproteinase 14; Middle Aged; Quinolines; Scavenger Receptors, Class E

We previously reported that colestimide, an anion exchange resin, improved glycemic control in patients with type 2 diabetes. However, the factors associated with the decrease of HbA1c remain unclear. In present study, we retrospectively compared glycemic control between groups receiving colestimide (n=71), atorvastatin (n=99), pravastatin (n=85), and pitavastatin (n=95) until 3 months after the start of treatment. In the colestimide group, fasting plasma glucose decreased significantly from 169 ± 59 to 138 ± 29 mg/dL after 3 months (P<0.01), and glycated hemoglobin (HbA1c) declined from 8.1 ± 1.0% to 7.4 ± 0.8% (an 8% reduction, P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin and pitavastatin groups. On the other hand, both parameters increased significantly in the atorvastatin group. Multivariate analysis revealed that baseline HbA1c was the main determinant of the decrease of HbA1c in the colestimide group while age, sex, BMI, and baseline lipid levels were not correlated with the effect of colestimide treatment. The decrease of HbA1c showed a positive correlation with baseline HbA1c (r=0.60, P<0.0001), and patients with a larger change of HbA1c (>8.4%) displayed a better response to colestimide. In conclusion, since patients with type 2 diabetes often have hyperlipidemia as well, colestimide therapy may have a clinically useful dual action in such patients. Baseline HbA1c has the most important independent influence on the glucose-lowering effect of colestimide.

Topics: Aged; Atorvastatin; Blood Glucose; Comorbidity; Diabetes Mellitus, Type 2; Epichlorohydrin; Female; Glycated Hemoglobin; Heptanoic Acids; Humans; Hypercholesterolemia; Hypoglycemic Agents; Imidazoles; Lipids; Male; Middle Aged; Multivariate Analysis; Pravastatin; Pyrroles; Quinolines; Resins, Synthetic; Retrospective Studies; Treatment Outcome

Topics: Analysis of Variance; Atorvastatin; Biomarkers; Cholesterol, LDL; Evidence-Based Medicine; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Patient Selection; Pyrimidines; Pyrroles; Quinolines; Rosuvastatin Calcium; Sulfonamides; Time Factors; Treatment Outcome

The primary objective was to assess the safety and tolerability of pitavastatin 4mg once daily during 52 weeks treatment. The secondary objectives were to assess the effect on lipid and lipoprotein fractions and ratios, and LDL-C target attainment.. Patients with primary hypercholesterolemia or combined dyslipidemia who had previously received pitavastatin, atorvastatin or simvastatin for 12 weeks during double-blind phase III studies received open-label pitavastatin 4mg once daily for up to 52 weeks.. Investigators at 72 sites enrolled 1353 patients who received at least one dose of pitavastatin 4mg; 155 (11.5%) patients discontinued treatment during the 52-week follow up. The proportion of patients achieving NCEP and EAS LDL-C targets at week 52 was 74.0% and 73.5% respectively. The reduction in LDL-C levels seen during the double-blind studies was sustained, while HDL-C levels rose continually during follow up, ultimately increasing by 14.3% over the initial baseline. Changes in other efficacy parameters (triglycerides, total cholesterol, non-HDL-C, Apo-A1 and Apo-B, high sensitivity C-reactive protein, oxidised LDL) and ratios (total cholesterol: HDL-C, non-HDL-C:HDL-C and Apo-B:Apo-A1) were sustained during 52-weeks treatment compared with the end of the double-blind studies. Pitavastatin was well tolerated: 4.1% of patients withdrew from the study due to treatment emergent adverse events (TEAEs) and none of the serious adverse events were considered treatment-related. No clinically significant abnormalities were associated with pitavastatin in routine laboratory variables, urinalysis, vital signs or 12-lead ECG. There were no reports of myopathy, myositis or rhabdomyolysis. The most common TEAEs were: increased creatine phosphokinase (5.8%), nasopharyngitis (5.4%) and myalgia (4.1%).. Pitavastatin 4mg once daily was effective and well tolerated during 52-weeks treatment in patients with primary hypercholesterolemia or combined dyslipidemia. Around three-quarters of patients achieved NCEP and EAS LDL-C targets at week 52, HDL-C levels rose continually during follow up, while changes in other efficacy parameters were sustained over the year-long study.

Topics: Cholesterol, HDL; Cholesterol, LDL; Drug Tolerance; Dyslipidemias; Enzyme Inhibitors; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Quinolines

It is not clear if the new 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pitavastatin prevents atherogenesis by a direct effect. Statins have a cholesterol-lowering effect, so an accessible animal model of atherosclerosis showing only moderate hypercholesterolaemia as in humans, is needed. The effects of pitavastatin were evaluated on atherosclerotic lesions accumulating foam cells derived from macrophages, produced in rabbits with moderate hypercholesterolaemia by chronic inhibition of nitric oxide synthase (NOS).. White New Zealand rabbits were fed a 0.2% cholesterol diet with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) in the same diet. Pitavastatin (0.1 and 0.3 mg x kg(-1)) was given orally once a day for 8 weeks. The aortic arch and thoracic aorta were analysed by histochemistry and atherosclerotic lesions were quantified. The effect of pitavastatin on adhesion of THP-1 cells to endothelial cells, and cholesterol content in RAW264.7 cells incubated with oxidized or acetylated LDL were also investigated.. Atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS. The area of atherosclerotic lesions was diminished by pitavastatin administration. The adhesion of THP-1 cells and cholesteryl ester content in RAW macrophages were decreased by pitavastatin treatment.. Atherosclerosis induced by chronic inhibition of NOS in moderately hypercholesterolaemic rabbits was suppressed by pitavastatin via inhibition of macrophage accumulation and macrophage foam cell formation.

Topics: Animals; Atherosclerosis; Cell Adhesion; Endothelium, Vascular; Enzyme Inhibitors; Humans; Hypercholesterolemia; Immunohistochemistry; Male; Monocytes; Nitric Oxide; Quinolines; Rabbits

In addition to the risk of progression to end-stage renal disease (ESRD), chronic kidney disease (CKD) is also known to be associated with an elevated risk of cardiovascular disease (CVD). Statins may improve renal function in CKD patients.. The database of the LIVALO Effectiveness and Safety (LIVES) Study, a large-scale (n=20,279), long-term (104 weeks), prospective post-marketing surveillance study of hypercholesterolemic patients treated with pitavastatin, was used to evaluate the effects of pitavastatin on the estimated glomerular filtration rate (eGFR).. Of the 19,925 patients enrolled in the aforementioned study, data from 3,119 patients were analyzed to evaluate the effects of pitavastatin treatment for 104 weeks on the eGFR. In this subanalysis, 958 patients with a baseline eGFR of less than 60 mL/min/1.73 m(2) (30.7%) were analyzed. A significant increase of the eGFR (+5.4 mL/min/1.73 m(2)) was observed after 104 weeks of pitavastain treatment (p < 0.001; one-sample t-test). In the analysis of the time-course of changes in the eGFR in response to pitavastatin treatment, the eGFR was elevated by 2.4 mL/min/1.73 m(2) after 12 weeks' treatment, and by 5.6 mL/min/1.73 m(2) after 104 weeks' treatment (p < 0.001; repeated measures ANOVA). The results of multivariate analysis identified the presence/absence of proteinuria and the amount change of HDL-C as clinical factors associated with increased eGFR during pitavastatin treatment.. Increased eGFR was noted after 104 weeks of treatment with pitavastatin, which suggests a possible effect of the statin on CKD.

Topics: Aged; Cholesterol, HDL; Data Collection; Female; Glomerular Filtration Rate; Humans; Hypercholesterolemia; Male; Middle Aged; Multivariate Analysis; Proteinuria; Quinolines; Renal Insufficiency, Chronic

Statins were first introduced in the 1980s as a treatment of hypercholesterolemia. They provide a remarkable array of clinical benefits, including the reduction of low-density lipoprotein cholesterol, total cholesterol, and triglycerides, and elevation of high-density lipoprotein cholesterol. The US Food and Drug Administration has recently approved a new statin-pitavastatin-for launch in 2010. In several clinical trials, pitavastatin has shown favorable clinical efficacy, a positive safety profile, and encouraging clinical experience in Japan and other parts of Asia.

Topics: Atorvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pravastatin; Product Surveillance, Postmarketing; Pyrroles; Quinolines; Simvastatin

The photostability of pitavastatin, an HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia, was investigated. The sample solution was exposed to UV-A radiation and the photodegradation process was monitored by means of spectrophotometric method and HPLC-DAD. Pitavastatin was shown to be photolabile and its photodegradation reaction followed the first-order kinetics with the rate constant k=3.54 x 10(-4)+/-9.43 x 10(-6)s(-1). The chromatograms revealed the presence of four major photoproducts (PP-1-PP-4). The separated and isolated photolytic products were identified using a mass spectrometer coupled with a time of flight (TOF) analyzer. The main reaction observed during exposure to radiation of pitavastatin was photocyclisation leading to formation of four-ring photoproducts.

Topics: Chromatography, High Pressure Liquid; Drug Stability; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Mass Spectrometry; Quinolines; Spectrophotometry, Ultraviolet; Ultraviolet Rays

Hypercholesterolemia has been identified as an important risk factor for stroke. It has been reported that statins might reduce the risk for new or recurrent cardiovascular events and strokes.. This paper reports on the effects of pitavastatin on cerebral blood flow in 2 elderly patients.. Two patients, a 72-year-old right-handed Japanese man and a 77-year-old right-handed Japanese woman, both with a history of cerebral infarction, received 6-month treatment with pitavastatin 2 mg/d for complicated hypercholesterolemia. To assess regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) studies with technetium-99m-ethyl cysteinate dimer were carried out before and after pitavastatin administration. Tomography was evaluated using the Easy z Score Imaging System. None of the patients' other treatments, with the exception of pitavastatin initiation, were modified during the treatment period. In both patients, serum total cholesterol concentrations were improved within 3 months of initiation of pitavastatin treatment, with no marked changes in clinical symptoms. In both patients, improvement was found in rCBF on SPECT. The z score of the left parietal lobe in 1 patient was improved, from 2.20 to 1.69. That of the other patient was also improved, from 2.42 to 1.94.. In both patients, clinically significant improvement in rCBF was found after 6-month treatment with pitavastatin 2 mg/d.

Topics: Aged; Cerebral Infarction; Cerebrovascular Circulation; Cholesterol; Cysteine; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Organotechnetium Compounds; Quinolines; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

To investigate the effect of pitavastatin on asymptomatic atherosclerosis in patients with hypercholesterolemia.. Thirty-five outpatients with hypercholesterolemia (61.5+/-12.8 yr) were administered 2 mg oral pitavastatin daily for 6 months. Plasma pentraxin 3 (PTX3), a novel inflammatory marker of atherosclerosis, was measured together with the serum hsCRP and carotid-artery intima-media thickness (IMT).. Significant improvement of the LDL-C/HDL-C and log (TG/HDL-C) ratios began to be observed from 1 month after using pitavastatin. Significant correlation of the initial PTX3 value was observed with the initial plaque score (PS) (p=0.038, r=0.246), but not between the hsCRP and plasma PTX3 or PS. When patients were divided into 3 groups based on the initial PTX3 values, a significant decrease of the plasma PTX3 was obtained in the highest PTX3 group alone (p=0.034). The change in the plasma PTX3 value (DeltaPTX3) was significantly correlated with the Delta mean IMT during the study period (p=0.008, r=0.456).. Pitavastatin significantly reduced the elevated plasma levels of PTX3 in patients with hypercholesterolemia by its pleiotropic effect against atherosclerotic inflammation. This study showed for the first time that the plasma PTX3 might be a useful blood parameter for direct detection of active atherosclerotic change.

Topics: Aged; Atherosclerosis; C-Reactive Protein; Female; Humans; Hypercholesterolemia; Inflammation; Male; Middle Aged; Quinolines; Serum Amyloid P-Component; Vascular Resistance

Low high-density lipoprotein cholesterol (HDL-C) is an important clinical risk factor for cardiovascular disease (CVD). Statins have been known to have a potent HDL-C-elevating effect in addition to low-density lipoprotein cholesterol (LDL-C)-lowering effects.. The database of LIVALO effectiveness and safety (LIVES) Study, a large-scale (n=20,279), long-term (104 weeks), prospective post-marketing surveillance of hypercholesterolemic patients treated with pitavastatin, was used to evaluate and analyze effects on plasma lipids, especially focusing on HDL-C.. Total cholesterol (TC) (-21.0%) and LDL-C (-31.3%) were significantly reduced. The decrease in triglyceride (TG) was significant in hypertriglyceridemic patients. HDL-C was elevated by 5.9% and 24.6% in all and in patients with low HDL-C levels (less than 40 mg/dL) at baseline, respectively (p<0.0001). In time-course analysis, elevation of HDL-C in the low HDL-C group was enhanced by 14.0% and 24.9% at 12 weeks and 104 weeks, respectively. A significant increase in HDL-C by pitavastatin treatment was also observed after switching from other statins. Multivariable analysis showed that BMI, diabetes, liver disease, and pre-treated other cholesterol-lowering drugs emerged as significant factors influencing HDL-C.. Pitavastatin had stable clinical effects on LDL-C, TG, and HDL-C for 104 weeks. It was noteworthy that HDL-C in patients with low HDL-C was continuously increased by this agent during the period tested.

Topics: Aged; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipoproteins, HDL; Male; Middle Aged; Multivariate Analysis; Product Surveillance, Postmarketing; Quinolines

We previously reported that glycemic control deteriorated in patients receiving atorvastatin, which is useful for the treatment of hypercholesterolemia in patients with type 2 diabetes. Pitavastatin has a strong lipid-lowering effect, comparable to that of atorvastatin, but it is unknown whether pitavastatin has an adverse influence on glycemic control. The aim of this study was to examine. The effects of three different statins (pravastatin, atorvastatin, and pitavastatin) on blood glucose and HbA(1C) levels in diabetic patients.. We retrospectively compared glycemic control between groups receiving atorvastatin (10 mg/day, group A, n=99), pravastatin (10 mg/day, group Pr, n=85), and pitavastatin (2 mg/day, group Pi, n=95) from the start of treatment until 3 months later. Patients were excluded if the dosage of their antidiabetic drugs was changed, if their drug therapy was altered within 3 months before starting statin therapy, or if events occurred that could affect glycemic control such as hospitalization.. The subjects available for analysis were 74 patients from group A, 71 patients from group Pr, and 74 patients from group Pi. Arbitrary blood glucose levels increased from 147+/-51 mg/dL (mean+/-SD) to 176+/-69 mg/dL in group A, but only changed minimally from 136+/-31 to 134+/-32 mg/dL in group Pr and from 155+/-53 to 154+/-51 mg/dL in group Pi. HbA(1C) increased from 7.0+/-1.1% to 7.4+/-1.2% in group A, while it was 6.9+/-0.9% versus 6.9+/-1.0% in group Pr, and 7.3+/-1.0% versus 7.2+/-1.0% in group Pi. There was no correlation between Delta LDL-C and Delta HbA(1C) (the change from baseline to 3 months) in any of the groups.. The glycemic parameters only increased significantly in group A, suggesting that pitava-statin and pravastatin did not have an adverse influence on glycemic control in type 2 diabetic patients.

Topics: Atorvastatin; Blood Glucose; Diabetes Mellitus, Type 2; Drug Evaluation; Glucose Intolerance; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pravastatin; Pyrroles; Quinolines; Retrospective Studies

Topics: Carotid Artery, Common; Compliance; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Treatment Outcome; Ventricular Function, Left

Resistin in serum is associated with high risk in patients with atherosclerosis. This clinical study aimed to investigate whether pitavastatin can regulate the serum level of resistin, together with levels of other inflammatory cytokines and adipocytokines.. Forty two outpatients (mean age 65.2 +/- 12.6 yr, M/F: 21/21) with hypercholesterolemia were administered 2 mg of pitavastatin and serum levels of resistin, together with serum levels of adiponectin, leptin, TNF-alpha and hsCRP, were measured before, and 12 weeks after enrollment.. There was no significant gender-related difference in initial serum resistin levels. Pitavastatin significantly decreased LDL-cholesterol after 12 weeks. Initial levels of resistin showed a significant correlation with those of hsCRP (r=0.38, p=0.013), but not TNF-alpha or HOMA-R. Serum resistin, but not adiponectin and leptin, levels were significantly decreased, dropping from 17.1 +/- 9.9 ng/ dL to 15.2+/-10.0 (p=0.001) after 12 weeks of administration. The patient group with a baseline hsCRP > or = 0.1 at enrollment (n=17) had decreased levels of both resistin and hsCRP (p=0.011 and p=0.022, respectively).. This study showed the pleiotropic effect of pitavastatin on the serum resistin concentration, suggesting that it may assist in the prevention of atherosclerosis.

Topics: Adiponectin; Aged; C-Reactive Protein; Female; Humans; Hypercholesterolemia; Leptin; Male; Middle Aged; Quinolines; Resistin; Tumor Necrosis Factor-alpha

Independent of their lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective effects on various models of progressive renal diseases, therefore, additional therapeutic advantages have been considered. In the present study, using spontaneously hypercholesterolaemic Imai rats, we examined the protective effects of pitavastatin on renal injuries and the oxidative modification of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized lipoproteins are speculated to be involved in the mechanism of this rat strain's renal injuries.. Male Imai rats were treated with pitavastatin (n = 11) at a dose of 100 mg/kg diet or received no specific therapy as controls (n = 11) from 10 to 22 weeks of age. Body weight, urinary protein excretion and serum constituents were evaluated every 4 weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and renal histology were examined.. Pitavastatin treatment did not affect hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine clearance deterioration. At the end of the study, lag times for LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126 and 153%, respectively, compared with the controlled group. The glomerulosclerosis index (SI) for untreated controlled rats was significantly higher than that for the pitavastatin-treated group. An immunohistochemistry study showed significantly lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in pitavastatin-treated rats compared with those controlled.. Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid-lowering effects. Prevention of oxidative modification of LDL and HDL may play an important role on the beneficial effects of pitavastatin treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Blood Urea Nitrogen; Deoxyguanosine; Enzyme Inhibitors; Hypercholesterolemia; Hyperlipidemias; Kidney; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Macrophages; Oxygen; Quinolines; Rats

Reactive oxygen species-scavenging enzyme Cu/Zn superoxide dismutase (SOD) regulated by peroxisome proliferator-activated receptors (PPARs) plays an important role in vascular responsiveness. However, it remains unknown whether statin restores vascular dysfunction through the activation of reactive oxygen species-scavenging enzymes in vivo. We hypothesized that pitavastatin restores vascular function by modulating oxidative stress through the activation of Cu/ZnSOD and PPAR-gamma in hypercholesterolemia. New Zealand White male rabbits were fed either normal chow or a 1% cholesterol (CHO) diet for 14 wk. After the first 7 wk, the CHO-fed rabbits were further divided into three groups: those fed with CHO feed only (HC), those additionally given pitavastatin, and those additionally given an antioxidant, probucol. The extent of atherosclerosis was assessed by examining aortic stiffness. When compared with the HC group, both the pitavastatin and probucol groups showed improved aortic stiffness by reducing aortic levels of reactive oxidative stress, nitrotyrosine, and collagen, without affecting serum cholesterol or blood pressure levels. Pitavastatin restored both Cu/ZnSOD activity (P < 0.005) and PPAR-gamma expression and activity (P < 0.01) and inhibited NAD(P)H oxidase activity (P < 0.0001) in the aorta, whereas probucol inhibited NAD(P)H oxidase activity more than did pitavastatin (P < 0.0005) without affecting Cu/ZnSOD activity or PPAR-gamma expression and activity. Importantly, Cu/ZnSOD activity was positively correlated with the PPAR-gamma activity in the aorta (P < 0.005), both of which were negatively correlated with aortic stiffness (P < 0.05). Vascular Cu/ZnSOD and PPAR-gamma may play a crucial role in the antiatherogenic effects of pitavastatin in hypercholesterolemia in vivo.

Topics: Animals; Anticholesteremic Agents; Aorta; Elasticity; Enzyme Inhibitors; Hypercholesterolemia; Immunohistochemistry; Male; Oxidative Stress; PPAR gamma; Probucol; Quinolines; Rabbits; Superoxide Dismutase

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Fatty Acids, Monounsaturated; Femoral Artery; Fluvastatin; Hindlimb; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Ischemia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic; Neovascularization, Physiologic; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pyridines; Quinolines

Topics: Animals; Cholesterol, LDL; Dogs; Drugs, Investigational; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Quinolines; Rats; Rats, Wistar