Effects of Pitavastatin in Japanese Patients With Chronic Heart Failure

Takano, Hiroyuki; Mizuma, Hiroshi; Kuwabara, Yoichi; Sato, Yasunori; Shindo, Satoshi; Kotooka, Norihiko; Fujimatsu, Daisuke; Kobayashi, Yoshio; Inoue, Teruo; Node, Koichi; Komuro, Issei

doi:10.1253/circj.cj-12-1062

Cited by 43 publications

(31 citation statements)

References 32 publications

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“…Thus, different inclusion and exclusion criteria could cause differences in the pathophysiological and etiological changes observed in heart failure, disturbing the consistence of the results in the cohort. Recently, prospective, randomized, open-label and blinded-endpoint PEARL study (14) of patients with mildly symptomatic heart failure demonstrated that pitavastatin could significantly reduce cardiac death or hospitalization in patients with LVEF ³ 30 %, but not in patients with LVEF 30 %. This outcome partly supported our results and provided important data on the role of pitavastatin in the treatment of chronic heart failure.…”

Section: Resultsmentioning

confidence: 99%

“…Pitavastatin has been reported to exert a preventive effect on pressure overload-induced heart failure (12) and ischemic heart failure (13). However, in a PEARL study (14), pitavastatin did not reduce cardiac death or hospitalization in patients with left ventricular ejection fraction (LVEF) < 30 %. Kjekshus (15) and Chang (16) also reported that statins did not reduce the number of deaths from any cause in patients with systolic heart failure.…”

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confidence: 99%

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Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Hu¹,

Jiang²

2014

Acta Pharmaceutica

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Dilated cardiomyopathy (DCM) is a multifactorial disease involving cardiac dysfunction and enlargement of one or of both ventricles (1). A number of new anti-heart failure medications, even cytokine therapy (2) or stem cell transplantation (3) have been developed (4) C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg -1 d -1 . After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca 2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA--2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT 1 R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT 1 R-PKCb2-Ca 2+ handling proteins.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

Hu¹,

Jiang²

2014

Acta Pharmaceutica

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“…In a study involving patients with dilated cardiomyopathy, 6 months of atorvastatin, but not rosuvastatin, improved cardiac MIBG scintigraphy parameters, LVEF, NT-proBNP and oxidized LDL-cholesterol concentrations [113]. In contrast, in a recently published 4-year follow-up of Japanese patients with chronic heart failure, pitavastatin, a lipophilic statin, at 2 mg/day (equivalent to simvastatin at approximately 20 mg/day or atorvastatin at approximately 10 mg/day) did not improve cardiac mortality and hospitalization for worsening heart failure [142]. Predefined subgroup analysis did demonstrate improvements in patients with a LVEF >30 %, suggesting a possible statin-ventricular function interaction.…”

Section: Do These Actions Influence Cardiovascular End Points?mentioning

confidence: 92%

Statins and the autonomic nervous system

Millar

Floras

2013

Clinical Science

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Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A 'pleiotropic' property of statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.

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“…1 As they noted in their letter, rosuvastatin treatment significantly reduced the primary endpoint in the subgroups of patients with lower amino-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (NT-proBNP <103 pmol/L) and higher high-sensitivity C-reactive protein (hsCRP) concentration (hsCRP ≥2.0 mg/L) in Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). 2, 3 Those papers were published in 2009 and so we could not know of the findings in 2006 when we started the Pitavastatin Heart Failure (PEARL) study.…”

mentioning

confidence: 96%