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Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

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Related in: MedlinePlus

Changes in carotid arterial stiffness in 30 patients with hypercholesterolaemia randomized to receive either pitavastatin (1–2 mg day−1, n= 15) or diet and exercise therapy for 12 months. Carotid ultrasonography was used to reveal end-systolic and end-diastolic diameters of the common carotid artery, Ds and Dd, respectively, and arterial stiffness, β, was calculated using the formula ln(SBP/DBP)/[(Ds – Dd)/Dd], where SBP and DBP are the systolic and diastolic blood pressures, respectively. *P < 0.05 vs. no statin group after treatment. Data from Mizuguchi et al. [102]. Baseline (□); 12 months (■)
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fig07: Changes in carotid arterial stiffness in 30 patients with hypercholesterolaemia randomized to receive either pitavastatin (1–2 mg day−1, n= 15) or diet and exercise therapy for 12 months. Carotid ultrasonography was used to reveal end-systolic and end-diastolic diameters of the common carotid artery, Ds and Dd, respectively, and arterial stiffness, β, was calculated using the formula ln(SBP/DBP)/[(Ds – Dd)/Dd], where SBP and DBP are the systolic and diastolic blood pressures, respectively. *P < 0.05 vs. no statin group after treatment. Data from Mizuguchi et al. [102]. Baseline (□); 12 months (■)

Mentions: Heart In an animal model of hypertensive heart failure, pitavastatin inhibits load-induced cardiac hypertrophy and fibrosis through inhibition of RhoA-ERK-serum response factor signalling [98, 99]. Pitavastatin reduces remodelling and improves ventricular function in rat hearts through increased eNOS production associated with PI3K signalling and a decrease in oxidative stress [100]. In the absence of eNOS in a mouse model, pitavastatin also reduced cardiac remodelling induced by angiotensin II and renal insufficiency through inhibition of the transforming growth factor-β-Smad signalling pathway by suppression of oxidative stress [67]. Similar results were obtained by Takuwa et al. [101], who showed that pitavastatin reduces cardiac remodelling, by inhibition of sphingosine kinase 1, and reduces oxidative stress in juvenile mice. Furthermore, in a 12 month randomized, controlled trial in 30 patients with hypercholesterolaemia and preserved left ventricular ejection fraction, treatment with pitavastatin (1 or 2 mg day−1, n= 15) for 1 year significantly reduced carotid arterial stiffness and significantly improved regional left ventricular systolic and diastolic function (P < 0.05) compared with patients given placebo (Figure 7) [102].


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Changes in carotid arterial stiffness in 30 patients with hypercholesterolaemia randomized to receive either pitavastatin (1–2 mg day−1, n= 15) or diet and exercise therapy for 12 months. Carotid ultrasonography was used to reveal end-systolic and end-diastolic diameters of the common carotid artery, Ds and Dd, respectively, and arterial stiffness, β, was calculated using the formula ln(SBP/DBP)/[(Ds – Dd)/Dd], where SBP and DBP are the systolic and diastolic blood pressures, respectively. *P < 0.05 vs. no statin group after treatment. Data from Mizuguchi et al. [102]. Baseline (□); 12 months (■)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376429&req=5

fig07: Changes in carotid arterial stiffness in 30 patients with hypercholesterolaemia randomized to receive either pitavastatin (1–2 mg day−1, n= 15) or diet and exercise therapy for 12 months. Carotid ultrasonography was used to reveal end-systolic and end-diastolic diameters of the common carotid artery, Ds and Dd, respectively, and arterial stiffness, β, was calculated using the formula ln(SBP/DBP)/[(Ds – Dd)/Dd], where SBP and DBP are the systolic and diastolic blood pressures, respectively. *P < 0.05 vs. no statin group after treatment. Data from Mizuguchi et al. [102]. Baseline (□); 12 months (■)
Mentions: Heart In an animal model of hypertensive heart failure, pitavastatin inhibits load-induced cardiac hypertrophy and fibrosis through inhibition of RhoA-ERK-serum response factor signalling [98, 99]. Pitavastatin reduces remodelling and improves ventricular function in rat hearts through increased eNOS production associated with PI3K signalling and a decrease in oxidative stress [100]. In the absence of eNOS in a mouse model, pitavastatin also reduced cardiac remodelling induced by angiotensin II and renal insufficiency through inhibition of the transforming growth factor-β-Smad signalling pathway by suppression of oxidative stress [67]. Similar results were obtained by Takuwa et al. [101], who showed that pitavastatin reduces cardiac remodelling, by inhibition of sphingosine kinase 1, and reduces oxidative stress in juvenile mice. Furthermore, in a 12 month randomized, controlled trial in 30 patients with hypercholesterolaemia and preserved left ventricular ejection fraction, treatment with pitavastatin (1 or 2 mg day−1, n= 15) for 1 year significantly reduced carotid arterial stiffness and significantly improved regional left ventricular systolic and diastolic function (P < 0.05) compared with patients given placebo (Figure 7) [102].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

Show MeSH
Related in: MedlinePlus