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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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Lack of correlation between stabilization of coronary plaques (expressed as reduction in yellow plaque content) and change in LDL-C in patients with coronary artery disease treated with pitavastatin 2 mg day−1 for 52 weeks. Intravascular ultrasound and coronary angiography were used to grade yellow atherosclerotic plaques and to assess their regression during treatment. Reproduced with permission from Kodama et al. [116]. LDL-C, low density lipoprotein cholesterol
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fig10: Lack of correlation between stabilization of coronary plaques (expressed as reduction in yellow plaque content) and change in LDL-C in patients with coronary artery disease treated with pitavastatin 2 mg day−1 for 52 weeks. Intravascular ultrasound and coronary angiography were used to grade yellow atherosclerotic plaques and to assess their regression during treatment. Reproduced with permission from Kodama et al. [116]. LDL-C, low density lipoprotein cholesterol

Mentions: Stabilization of vulnerable carotid plaques was seen within 1 month of treatment with pitavastatin 4 mg day−1 in 33 patients with acute coronary syndrome in a placebo-controlled trial (Figure 9) [114]. In the JAPAN-ACS (Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome) study, a significant (P < 0.001) reduction in coronary plaque volume was seen in 111 patients given pitavastatin 4 mg day−1 for 8–12 months. The decrease in plaque volume with pitavastatin was similar to that seen in 115 patients treated with atorvastatin 20 mg day−1 (−16.9 ± 13.9% vs.−18.1 ± 14.2%) [115]. Stabilization of coronary plaques, determined by colour angioscopy, occurred following treatment with pitavastatin 2 mg day−1 for 52 weeks in patients with CAD. This stabilization was not correlated with changes in LDL-C, suggesting a direct contribution of pleiotropic effects unrelated to cholesterol reduction (Figure 10) [116]. Such angioscopic regression has also been reported with atorvastatin in a previous report but, in contrast to the pitavastatin study, a correlation was observed between changes in the mean angioscopic (yellow) score for plaque stabilization and the change in LDL-C concentrations [117]. Furthermore, in another study, reductions in angioscopic score were correlated with subsequent changes in atheroma volume, measured by intravascular ultrasound, considered to reflect an improvement in plaque vulnerability [118].


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Lack of correlation between stabilization of coronary plaques (expressed as reduction in yellow plaque content) and change in LDL-C in patients with coronary artery disease treated with pitavastatin 2 mg day−1 for 52 weeks. Intravascular ultrasound and coronary angiography were used to grade yellow atherosclerotic plaques and to assess their regression during treatment. Reproduced with permission from Kodama et al. [116]. LDL-C, low density lipoprotein cholesterol
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig10: Lack of correlation between stabilization of coronary plaques (expressed as reduction in yellow plaque content) and change in LDL-C in patients with coronary artery disease treated with pitavastatin 2 mg day−1 for 52 weeks. Intravascular ultrasound and coronary angiography were used to grade yellow atherosclerotic plaques and to assess their regression during treatment. Reproduced with permission from Kodama et al. [116]. LDL-C, low density lipoprotein cholesterol
Mentions: Stabilization of vulnerable carotid plaques was seen within 1 month of treatment with pitavastatin 4 mg day−1 in 33 patients with acute coronary syndrome in a placebo-controlled trial (Figure 9) [114]. In the JAPAN-ACS (Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome) study, a significant (P < 0.001) reduction in coronary plaque volume was seen in 111 patients given pitavastatin 4 mg day−1 for 8–12 months. The decrease in plaque volume with pitavastatin was similar to that seen in 115 patients treated with atorvastatin 20 mg day−1 (−16.9 ± 13.9% vs.−18.1 ± 14.2%) [115]. Stabilization of coronary plaques, determined by colour angioscopy, occurred following treatment with pitavastatin 2 mg day−1 for 52 weeks in patients with CAD. This stabilization was not correlated with changes in LDL-C, suggesting a direct contribution of pleiotropic effects unrelated to cholesterol reduction (Figure 10) [116]. Such angioscopic regression has also been reported with atorvastatin in a previous report but, in contrast to the pitavastatin study, a correlation was observed between changes in the mean angioscopic (yellow) score for plaque stabilization and the change in LDL-C concentrations [117]. Furthermore, in another study, reductions in angioscopic score were correlated with subsequent changes in atheroma volume, measured by intravascular ultrasound, considered to reflect an improvement in plaque vulnerability [118].

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