pitavastatin and Cardiovascular-Diseases

A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy.. The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members.. We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects.. In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe.. The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.

Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metabolic Syndrome; Pravastatin; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Simvastatin

Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.. Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins.  Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects.  SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.. RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.. Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.. Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.. Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.

Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides

Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin.. A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high.. Blood lipid test showed mixed dyslipidemia.. Atorvastatin 10 mg/day was given to the patient.. The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin.. This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.

Topics: Alanine Transaminase; Alkaline Phosphatase; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; gamma-Glutamyltransferase; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Quinolines; Withholding Treatment

Observational studies and meta-analyses of randomized clinical trials data have revealed a 10-12% increased risk of new-onset diabetes (NOD) associated with statin therapy; the risk is increased with intensive treatment regimens and in people with features of the metabolic syndrome or prediabetes. The purpose of this review is to provide an updated summary of what is known about the potential mechanisms for the diabetogenic effect of statins.. Hydroxyl methyl glutaryl coenzyme A reductase (HMGCoAR) is the target of statin therapy and the activity of this key enzyme in cholesterol synthesis is reduced by statins in a partial and reversible way. Mendelian randomization studies suggest that the effect of statins on glucose homeostasis reflect reduced activity of HMGCoAR. In vitro and in vivo data indicate that statins reduce synthesis of mevalonate pathway products and increase cholesterol loading, leading to impaired β-cell function and decreased insulin sensitivity and insulin release. While this effect has been thought to be a drug class effect, recent insights suggest that pravastatin and pitavastatin could exhibit neutral effects on glycaemic parameters in patients with and without diabetes mellitus. The mechanisms by which statins might lead to the development of NOD are unclear. The inhibition of HMGCoAR activity by statins appears to be a key mechanism. It is difficult to offer a comprehensive view regarding the diabetogenic effect of statins because our understanding of the most widely recognized potential mechanisms, i.e. underlying statin-induced reduction of insulin sensitivity and/or insulin secretion, is still far from complete. The existence of this dual mechanism is supported by the results of a study in a large group of non-diabetic men, showing that a 46% higher risk of NOD in statin users compared to non-users was accompanied by a significant 12% reduction in insulin secretion and a 24.3% increase in insulin resistance. Although statin therapy is associated with a modest increase in the risk of NOD (about one per thousand patient-years), patients should be reassured that the benefits of statins in preventing cardiovascular disease (CVD) events far outweigh the potential risk from elevation in plasma glucose.

Topics: Aged; Animals; Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Insulin; Male; Metabolic Syndrome; Mice; Middle Aged; Pravastatin; Quinolines; Risk Factors

Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD.. The authors performed a systematic review and meta-analysis of all clinical trials exploring the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.. Six eligible studies comprising 7 treatment arms were selected for this meta-analysis. Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95% CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out sensitivity analysis.. This meta-analysis of all available clinical trials revealed a significant increase of FMD induced by pitavastatin.

Topics: Cardiovascular Diseases; Cholesterol, LDL; Databases, Factual; Dyslipidemias; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines; Risk Factors

Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit. Statins, that are the most used lipid-lowering drugs, can also increase HDL-C levels, although this effect is highly variable among studies and statins; the most recent developed statin, pitavastatin, beside its role as LDL-C-lowering agent, increases HDL-C levels at a significantly higher extent and progressively upon treatment; such increase was observed also when patients where shifted from another statin to pitavastatin. The stratification by baseline HDL-C levels revealed that only pitavastatin significantly increased HDL-C levels in patients with baseline HDL-C ≤45 mg/dl, while no changes were observed in patients with higher baseline HDL-C levels. In the last years the hypothesis that functional properties of HDL may be more relevant than HDL-C levels has risen from several observations. The treatment with pitavastatin not only increased HDL-C levels, but also increased the phospholipid content of HDL, increased the HDL efflux capacity and their anti-oxidant properties. These observations suggest that, besides its high LDL-C-lowering effect, pitavastatin also exhibits a significantly higher ability to increase HDL-C levels and may also positively affect the quality and functionality of HDL particles.

Topics: Animals; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines; Risk Factors; Treatment Outcome; Up-Regulation

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

The effect of statin therapy on plasma adiponectin levels has not been conclusively studied. Therefore, we aimed to evaluate this effect through a systematic review and meta-analysis of available randomized controlled trials (RCTs).. Quantitative data synthesis was performed using a random-effects model with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.. In 30 studies (43 study arms) with 2953 participants, a significant increase in plasma adiponectin levels was observed after statin therapy (WMD: 0.57 μg/mL, 95% CI: 0.18, 0.95, p = 0.004). In subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and pitavastatin were found to change plasma adiponectin concentrations by 0.70 μg/mL (95% CI: -0.26, 1.65), 0.50 μg/mL (95% CI: -0.44, 1.45), -0.70 μg/mL (95% CI: -1.08, -0.33), 0.62 μg/mL (95% CI: -0.12, 1.35), and 0.51 μg/mL (95% CI: 0.30, 0.72), respectively. With respect to duration of treatment, there was a significant increase in the subset of trials lasting ≥12 weeks (WMD: 0.88 μg/mL, 95% CI: 0.19, 1.57, p = 0.012) but not in the subset of <12 weeks of duration (WMD: 0.18 μg/mL, 95% CI: -0.23, 0.58, p = 0.390). Random-effects meta-regression suggested a significant association between statin-induced elevation of plasma adiponectin and changes in plasma low density lipoprotein cholesterol levels (slope: 0.04; 95% CI: 0.01, 0.06; p = 0.002).. The meta-analysis showed a significant increase in plasma adiponectin levels following statin therapy. Although statins are known to increase the risk for new onset diabetes mellitus, our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression.

Topics: Adiponectin; Adult; Aged; Atorvastatin; Cardiovascular Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pravastatin; Quinolines; Randomized Controlled Trials as Topic; Regression Analysis; Rosuvastatin Calcium; Simvastatin

The term cardiometabolic disease encompasses a range of lifestyle-related conditions, including Metabolic syndrome (MetS) and type 2 diabetes (T2D), that are characterized by different combinations of cardiovascular (CV) risk factors, including dyslipidemia, abdominal obesity, hypertension, hyperglycemia/insulin resistance, and vascular inflammation. These risk factors individually and interdependently increase the risk of CV and cerebrovascular events, and represent one of the biggest health challenges worldwide today. CV diseases account for almost 50% of all deaths in Europe and around 30% of all deaths worldwide. Furthermore, the risk of CV death is increased twofold to fourfold in people with T2D. Whilst the clinical management of CV disease has improved in Western Europe, the pandemic of obesity and T2D reduces the impact of these gains. This, together with the growing, aging population, means the number of CV deaths is predicted to increase from 17.1 million worldwide in 2004 to 23.6 million in 2030. The recommended treatment for MetS is lifestyle change followed by treatment for the individual risk factors. Numerous studies have shown that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D or MetS. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one-third, which leaves substantial residual risk. Recent studies suggest that low high-density lipoprotein-cholesterol (HDL-C) (<1 .0 mmol/l; 40 mg/dl) and high triglyceride levels (≥1.7 mmol/l; 150 mg/dl) are independent risk factors for CV disease and that the relationship between HDL-C and CV risk persists even when on-treatment LDL-C levels are low (<1.7 mmol/l; 70 mg/dl). European guidelines highlight the importance of reducing residual risk by targeting these risk factors in addition to LDL-C. This is particularly important in patients with T2D and MetS because obesity and high levels of glycated hemoglobin are directly related to low levels of HDL-C and high triglyceride. Although most statins have a similar low-density lipoprotein-lowering efficacy, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects (for example, high-density lipoprotein-elevating efficacy), adverse event profiles, and drug-drug interactions. The choice of statin should therefore depend on the needs of the indivi

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Metabolic Syndrome; Patient Selection; Quinolines; Risk Factors; Treatment Outcome

Statins effectively lower low-density lipoprotein-cholesterol (LDL-C) and reduce cardiovascular risk in people with dyslipidemia and cardiometabolic diseases such as Metabolic syndrome (MetS) or type 2 diabetes (T2D). In addition to elevated levels of LDL-C, people with these conditions often have other lipid-related risk factors, such as high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and a preponderance of highly atherogenic, small, dense low-density lipoprotein particles. The optimal management of dyslipidemia in people with MetS or T2D should therefore address each of these risk factors in addition to LDL-C. Although statins typically have similar effects on LDL-C levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects, adverse event profiles and drug-drug interactions. The choice of statin should therefore depend on the characteristics and needs of the individual patient. Compared with other statins, pitavastatin has distinct pharmacological features that translate into a broad range of actions on both apolipoprotein-B-containing and apolipoprotein-A-containing lipoproteins. Studies show that pitavastatin 1 to 4 mg is well tolerated and significantly improves LDL-C and triglyceride levels to a similar or greater degree than comparable doses of atorvastatin, simvastatin or pravastatin, irrespective of diabetic status. Moreover, whereas most statins show inconsistent effects on HDL-C levels, pitavastatin-treated patients routinely experience clinically significant elevations in HDL-C that are maintained and even increased over the long term. In addition to increasing high-density lipoprotein quantity, pitavastatin appears to improve high-density lipoprotein function and to slow the progression of atherosclerotic plaques by modifying high-density lipoprotein-related inflammation and oxidation, both of which are common in patients with MetS and T2D. When choosing a statin, it is important to note that patients with MetS have an increased risk of developing T2D and that some statins can exacerbate this risk via adverse effects on glucose regulation. Unlike many statins, pitavastatin appears to have a neutral and even beneficial effect on glucose regulation, making it a useful treatment option in this high-risk group of patients. Together with pitavastatin's beneficial effects on the cardiometabolic lipid profile and its low potential for drug-drug interac

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Metabolic Syndrome; Patient Selection; Quinolines; Risk Factors; Treatment Outcome

Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n = 33,040) showed that, although intensive versus standard glycaemic control significantly reduced CV events in people with T2D, the reduction was less than that achieved with lipid-lowering or antihypertensive treatment. Furthermore, fasting plasma glucose (FPG) concentrations were a modest predictor for CV risk in people without T2D. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. Reducing low-density lipoprotein-cholesterol levels using statins significantly reduces CV risk in people with and without T2D. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Based on recent clinical trial data, the US Food and Drug Administration have changed the labelling of all statins to include 'an effect of statins on incident diabetes and increases in haemoglobin A1c and/or FPG'. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. Mechanisms explaining the potentially higher incidence of T2D with statin therapy have not been confirmed. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Moreover, although some statins (for example, atorvastatin) are associated with increased haemoglobin A1c levels in patients receiving intensive but not moderate therapy, other statins (for example, pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without T2D or metabolic syndrome. The potential diabetogenic effects of statins may therefore differ between drugs. In conclusion, conflicting data exist regarding the diabetogenic effects of statins. Further studies are required to understand whether all statins have the same effect and whether some patient groups are at higher risk than others. Meanwhile, results suggest that the net CV benefit favours the use of statin therapy in patients with dyslipidaemia, irrespective of T2D risk.

Topics: Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Metabolic Syndrome; Patient Selection; Quinolines; Risk Factors; Treatment Outcome

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

Topics: Cardiovascular Diseases; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Musculoskeletal Pain; 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

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

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

The risk of cardiovascular disease is increased among persons with human immunodeficiency virus (HIV) infection, so data regarding primary prevention strategies in this population are needed.. In this phase 3 trial, we randomly assigned 7769 participants with HIV infection with a low-to-moderate risk of cardiovascular disease who were receiving antiretroviral therapy to receive daily pitavastatin calcium (at a dose of 4 mg) or placebo. The primary outcome was the occurrence of a major adverse cardiovascular event, which was defined as a composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause.. The median age of the participants was 50 years (interquartile range, 45 to 55); the median CD4 count was 621 cells per cubic millimeter (interquartile range, 448 to 827), and the HIV RNA value was below quantification in 5250 of 5997 participants (87.5%) with available data. The trial was stopped early for efficacy after a median follow-up of 5.1 years (interquartile range, 4.3 to 5.9). The incidence of a major adverse cardiovascular event was 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.48 to 0.90; P = 0.002). Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 participants (5.3%) and in 155 (4.0%), respectively.. Participants with HIV infection who received pitavastatin had a lower risk of a major adverse cardiovascular event than those who received placebo over a median follow-up of 5.1 years. (Funded by the National Institutes of Health and others; REPRIEVE ClinicalTrials.gov number, NCT02344290.).

Topics: Cardiovascular Diseases; Double-Blind Method; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Myocardial Infarction; Quinolines

To clarify the mechanism by which pitavastatin reduced cardiovascular (CV) events more effectively than atorvastatin in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), the changes in (Δ) non-heparinized serum level of lipoprotein lipase mass (LPL mass) during administration of the respective statins were investigated.. From TOHO-LIP data, 223 hypercholesterolemic patients with any CV risks followed at Toho University Sakura Medical Center were analyzed. The patients were randomized to pitavastatin (2 mg/day) group (n=107) or atorvastatin (10 mg/day) group (n=116), and followed for 240 weeks. In this subgroup study, the primary and secondary end points were the same as those in TOHO-LIP, and 3-point major adverse cardiovascular events (3P-MACE) was added. The relationship between ΔLPL mass during the first year and the incidences of each end point was analyzed.. Pitavastatin administration reduced CV events more efficaciously than atorvastatin despite similar LDL cholesterol-lowering effect of the two statins. Increased LPL mass during the first year by pitavastatin treatment may be associated with this efficacy.

Topics: Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipase; Lipoprotein Lipase; Pyrroles; Quinolines

In the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), a multicenter randomized controlled trial, pitavastatin significantly reduced cardiovascular (CV) events compared to atorvastatin in patients with hypercholesterolemia. To investigate the mechanism by which pitavastatin preferentially prevents CV events, we investigated the relationship between CV events and cardio-ankle vascular index (CAVI) using the TOHO-LIP database.. For the subgroup analysis, we selected patients from a single center, Toho University Sakura Medical Center. After excluding those who had CV events at baseline or during the first year, 254 patients were enrolled. The primary end point was the same as that of TOHO-LIP, and three-point major cardiac adverse events (3P-MACE) was added as secondary end point.. The cumulative 5-year incidence of 3P-MACE (pitavastatin 1.6%, atorvastatin 6.1%, P=0.038) was significantly lower in pitavastatin group (2 mg/day) than in atorvastatin group (10 mg/day). CAVI significantly decreased only in pitavastatin group during the first year (9.50-9.34, P=0.042), while the change in low-density lipoprotein cholesterol (LDL-C) did not differ between the two groups. The change in CAVI during the first year positively correlated with 3P-MACE and tended to be an independent predictor of 3P-MACE in Cox proportional hazards model (hazard ratio, 1.736; P=0.079). The annual change in CAVI throughout the observation period was significantly higher in subjects with CV events compared to those without.. In this subgroup analysis, the reduction in CV events tended to be associated with the CAVI-lowering effect of pitavastatin, which was independent of the LDL-C-lowering effect.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cardio Ankle Vascular Index; Cardiovascular Diseases; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Quinolines

It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction.. The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m. Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

Topics: Aged; Angina, Stable; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Coronary Artery Disease; Female; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Prospective Studies; Quinolines; 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

This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events.. The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. The entire cohort was divided into three groups according to tertiles of HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, HDL-C >43, <53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups.. The primary endpoint event occurred in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively, and its incidence was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19-1.9; p = 0.001). Irrespective of the treatment regimen, Group 1 had significantly higher rates of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12-2.22; p = 0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05-1.98; p = 0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Multivariate analysis revealed that lower body mass index, prevalence of diabetes mellitus, higher levels of high-sensitivity C reactive protein at baseline, and lower levels of HDL-C at 3-month follow-up were independent predictors of the incidence of primary endpoint.. Lower levels of HDL-C at 3-month follow-up are independently associated with higher incidence of cardiovascular events in ACS patients receiving contemporary lipid-lowering therapy.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Cholesterol, HDL; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Quinolines; Treatment Outcome

Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.. To date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.. REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.

Topics: Adult; Aged; Anti-HIV Agents; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Female; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Primary Prevention; Prospective Studies; Quinolines; Risk Factors

The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).. The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.. In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.. ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Topics: Atorvastatin; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Clinical Protocols; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Metabolic Syndrome; Prospective Studies; Quinolines; Republic of Korea; Research Design; Risk Factors; Time Factors; Treatment Outcome

Dyslipidaemia and central obesity are the major factors underlying the dramatic increase in metabolic syndrome (MS). We compared the effects of early combined therapy with pitavastatin and intensive lifestyle modification (LSM) on the amelioration of each component of MS with those of LSM only.. PROPIT (a PROspective comparative clinical study to evaluate the efficacy and safety of PITavastatin in patients with metabolic syndrome) was a prospective, randomized, multicenter open-label 48-week trial. We enrolled 187 patients with MS (central obesity and prediabetes) and randomized them into two treatment groups: 2 mg pitavastatin daily + intensive LSM or intensive LSM only. The primary outcome was the improvements in the components of MS and in the percentage of non-MS converters.. After 1 year treatment, the improvement of MS score was significantly higher in the pitavastatin + LSM group (P = 0·039). However, non-MS converters (MS score ≤2) did not differ between the groups. The secondary outcomes, namely lipid profiles, the Apo B/A1 ratio, visceral fat/subcutaneous fat ratio and the Framingham risk score, were significantly improved in the pitavastatin group. There was no deterioration in glucose metabolism after treatment with pitavastatin for 1 year.. Early statin treatment can be an effective option in obese patients with MS, prediabetes and mild dyslipidaemia with further improvement of cardiovascular risk factors. We could not observe the increase rate of glucose intolerance in statin group. Future longitudinal studies are needed to test the benefits of early statin treatment compared with LSM.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; Cardiovascular Diseases; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Lipids; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Quinolines; Risk Factors; Treatment Outcome; Young Adult

To assess the safety and efficacy of pitavastatin in children and adolescents with hyperlipidemia.. A total of 106 children and adolescents with hyperlipidemia, ages 6 to 17 years, were enrolled in a 12-week randomized, double-blind, placebo-controlled study and randomly assigned to pitavastatin 1 mg, 2 mg, 4 mg, or placebo. During a 52-week extension period, subjects were up-titrated from 1 mg pitavastatin to a maximum dose of 4 mg in an effort to achieve an optimum low-density lipoprotein cholesterol (LDL-C) treatment target of <110 mg/dL (2.8 mmol/L). Adverse events rates, including abnormal clinical laboratory variables, vital signs, and physical examination were assessed.. Compared with placebo, pitavastatin 1, 2, and 4 mg significantly reduced LDL-C from baseline by 23.5%, 30.1%, and 39.3%, respectively, and in the open-label study 20.5% of the subjects reached the LDL-C goal <110 mg/dL (2.8 mmol/L). No safety issues were evident.. Pitavastatin at doses up to 4 mg is well tolerated and efficacious in children and adolescents aged 6-17 years.. Registered with EudraCT 2011-004964-32 and EudraCT 2011-004983-32.

Topics: Adolescent; Age Factors; Apolipoproteins; Cardiovascular Diseases; Child; Cholesterol; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Quinolines; Risk Factors; Treatment Outcome; Triglycerides

Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk. However, some patients show symptoms of coronary heart disease (CHD) even though their LDL-C is strictly controlled. Therefore, it is important to treat other risk factors.. Some 129 outpatients with dyslipidemia who were treated with either atorvastatin 10 mg/day (ATO), pitavastatin 2 mg/day (PIT), or rosuvastatin 2.5 mg/day (ROS) were enrolled. After informed consent was obtained, these patients were switched to another statin. Lipid profiles and lipoprotein fraction by polyacrylamide gel electrophoresis (PAGE) were compared between before and after 3 months of treatment with non-fasting blood sample.. LDL-C did not show any significant changes after switching and was maintained around 2.59 mmol/L in all groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in group ATO→PIT (1.43→1.54 mmol/L, p = 0.0010) and ROS→PIT (1.46→1.57 mmol/L, p = 0.0004), and was significantly decreased in group PIT→ATO (1.44→1.36 mmol/L, p = 0.0290). Apolipoprotein A-I (Apo A-I) and preheparin lipoprotein lipase (LPL) mass showed similar changes in HDL-C. Changes in HDL-C showed a significant positive correlation with those in Apo A-I and preheparin LPL mass, and a little but significant negative correlation with changes in Lp(a) and intermediate density lipoprotein (IDL) fraction.. ATO, PIT, and ROS have comparable effect on LDL-C lowering. Changes in HDL-C were similar to those in Apo A-I and preheparin LPL mass, and PIT was the most effective treatment in increasing HDL-C, Apo A-I, and preheparin LPL mass.

Topics: Aged; Aged, 80 and over; Apolipoprotein A-I; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein Lipase; Male; Middle Aged; Pyrimidines; Pyrroles; Quinolines; Risk Factors; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome

The TRUTH trial demonstrated that 8-month statin therapy alters the composition of coronary artery plaque using virtual histology (VH)-intravascular ultrasound (IVUS). The extended TRUTH study was conducted to evaluate the relationship between changes in coronary atherosclerosis and mid-term clinical outcomes and identify the factors associated with cardiovascular events.. Of 164 patients with angina pectoris who participated in the TRUTH trial, 119 subjects with analyzable IVUS data at both enrollment and the 8-month follow-up were enrolled and observed for at least two years. The primary end point was the time to first occurrence of cardiovascular composite events, including cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, unstable angina and ischemic-driven revascularization, except for target lesion revascularization.. The frequency of reaching the primary end point was 13% (16/119), with a mean follow-up period of 41.9±9.4 months. Although plaque regression and changes in plaque composition were not associated with future cardiovascular events, the serum high-sensitivity C-reactive protein (hs-CRP) levels at the start of the extended TRUTH study were significantly higher in the event group than in the event-free group (1.43 mg/L vs. 0.58 mg/L, p=0.01). A multivariate logistic regression analysis showed that the hs-CRP level was an independent significant predictor of cardiovascular events (odds ratio: 1.69; 95% confidence interval: 1.14-2.50, p=0.01).. Coronary artery plaque regression and changes in plaque composition during statin therapy do not predict future cardiovascular events in patients with angina pectoris. Instead, the serum hs-CRP level can be used as a predictor of cardiovascular events.

Topics: Aged; Angina Pectoris; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemia; Japan; Male; Middle Aged; Myocardial Infarction; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Regression Analysis; Risk Factors; Treatment Outcome; Ultrasonography, Interventional

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

Although statins vary in their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) levels, there is little evidence that the degree of these changes can explain cardiac risk reduction in Japan. Our objective was to compare the efficacy of statins on serum lipid levels and to explore the association between those changes and cardiac events in patients after percutaneous coronary intervention (PCI).. The 743 consecutive patients who underwent PCI from 2001 to 2008 were retrospectively investigated. Treatment with either atorvastatin or pitavastatin significantly reduced LDL-C compared with pravastatin or no statin. In contrast, only pitavastatin treatment significantly increased HDL-C (13.4 ± 22.9%, P=0.01 vs. no statin). Each statin significantly prevented major adverse cardiac events (MACE) compared with no statin, and pitavastatin was the most effective of all. Multivariate-adjusted analysis revealed that percent changes of both LDL-C and HDL-C independently predicted the incidence of MACE (hazard ratio [HR]: 1.015; 95% confidence interval [CI]: 1.010-1.020, HR: 0.988; 95%CI: 0.981-0.996, respectively). This relationship was preserved in patients with a baseline HDL-C level ≤ 45 mg/dl, but not HDL-C level > 45 mg/ml.. The extent of changes in LDL-C and HDL-C with statin treatment would independently alter the risk of cardiac events in Japanese patients for secondary prevention. Statins with varying lipid-modifying ability might provide differing prognosis in patients after PCI.

Topics: Aged; Aged, 80 and over; Angioplasty; Asian People; Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Postoperative Complications; Pyrroles; Quinolines; Retrospective Studies; Risk Factors

The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients.. Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up.. At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE.. Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS.

Topics: Acute Coronary Syndrome; Adiponectin; Aged; Angioplasty, Balloon, Coronary; Atorvastatin; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Coronary Vessels; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Logistic Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Pyrroles; Quinolines; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography, Interventional; Up-Regulation

Topics: Cardiovascular Diseases; HIV Infections; Humans; Quinolines

Grinspoon SK, Fitch KV, Zanni MV, et al; REPRIEVE Investigators.

Topics: Adult; Cardiovascular Diseases; HIV Infections; Humans; Quinolines

Topics: Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Topics: Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Topics: Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Topics: Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Topics: Cardiovascular Diseases; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Cardiovascular diseases are responsible for the majority of deaths on a global scale. Atherosclerosis is the main risk factor for cardiovascular disorders and represents a complex phenomenon associated with endothelial dysfunction and inflammation. Statins, especially atorvastatin (ATV) and pitavastatin (PTV), are common agents used to control ongoing atherosclerotic events in the body to minimize cardiovascular disease-based deaths.. The present study aimed at comparing the efficacy of ATV and PTV in a cell line model of inflammation. Human saphenous vein cells were treated with TNF-alpha to mimic atherosclerotic conditions, and the cells were divided into 7 groups, including control, DMSO, TNF-alpha (10 ng/mL-6 hours), ATV (50 μM/24 hours), PTV (2 μM/24 hours), ATV (50 μM/24 hours)+TNF-alpha (10 ng/mL-6 hours) and PTV (2 μM/24 hours)+TNF-alpha (10 ng/mL-6 hours). The expression levels of 20 proinflammatory cytokines and chemokines were investigated in these groups using a human atherosclerosis antibody array.. Possible pathway interactions were determined by STRING and PANTHER analyses. Comparison with the effect of ATV indicated that PTV reduced the levels of 4 proinflammatory cytokines: CCL11, CSF2, CCL20, and TGFB1 (p<0.05).. Pleiotropic effects of pitavastatin against cardiovascular diseases appeared to be better; however, additional studies are required to compare statins and to identify new drugs that maintain broader protection from the risks of cardiovascular diseases.

Topics: Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Cytokines; Endothelial Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Pilot Projects; Quinolines; Saphenous Vein; Tumor Necrosis Factor-alpha

Topics: Atorvastatin; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein Lipase; Pyrroles; Quinolines

Topics: Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

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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

Topics: Atorvastatin; Cardiovascular Diseases; China; Dyslipidemias; Glucose; Glycated Hemoglobin; Humans; Hypertension; Prediabetic State; Quinolines; Risk Factors

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Humans; Prospective Studies; Quinolines; Risk Factors

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

Managing dyslipidaemia is central to the management of cardiovascular disease. Statins are the cornerstone of cardiovascular prevention for general population, and in patients with type 2 diabetes mellitus. However, statin therapy predisposes to type 2 diabetes, particularly in patients with predisposition to this condition. Some statins have been associated with increases in blood glucose in patients, and others have shown to have neutral effects, varying from one another their glucose or diabetogenic capacity. Pitavastatin is a new member of the statin class. And 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.

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies.. We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention.. Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction.. Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.

Topics: Animals; Cardiovascular Diseases; Cell Proliferation; Collateral Circulation; Female; Hindlimb; Immunohistochemistry; Ischemia; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neovascularization, Pathologic; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Physical Conditioning, Animal; Quinolines; Renin; Risk Factors; Time Factors

Lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce cardiovascular (CV) risk in patients with dyslipidemia. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one third, which leaves a substantial residual risk. The Emerging Risk Factors Collaboration has shown that low levels of high-density lipoprotein-C (HDL-C) are independent risk factors for CV disease. It is therefore important that treatment strategies for dyslipidemia should target HDL-C in addition to LDL-C. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means. Therapeutic strategies include niacin, fibrates, thiazolidinediones, apolipoprotein A1 mimetics, cholesteryl ester transfer protein inhibitors, statins and combinations thereof. In general, statins produce inconsistent increases in HDL-C. However, pitavastatin, a new member of the statin family that was launched in 2003, and rosuvastatin consistently elicit marked increases in HDL-C that are sustained over time. This supplement will discuss the contribution of HDL-C as a possible predictor and modifiable risk factor for CV disease and will examine the potential role for pitavastatin in reducing residual CV risk.

Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Multicenter Studies as Topic; Quinolines; Risk Factors