Basic Science Review Section: Statin Therapy—Part II: Clinical Considerations for Cardiovascular Disease

Sadowitz, Benjamin; Seymour, Keri A.; Costanza, Michael J.; Gahtan, Vivian

doi:10.1177/1538574410363833

Cited by 21 publications

(13 citation statements)

References 135 publications

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“…Such effects can include improvements in endothelial function, decreases in smooth muscle proliferation and vascular inflammation and antiplatelet actions (Table 1), as well as effects on other lipids and lipoproteins [2–4]. Pleiotropic effects may play an important part in reducing cardiovascular mortality and morbidity [3], and differences in the spectrum of such effects between members of the class could be relevant when formulating management plans for individual patients. Furthermore, different enzymes are involved in the metabolism of different statins, leading to unique drug–drug interaction profiles.…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic effects of pitavastatin

Davignon

2012

Brit J Clinical Pharma

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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.

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Section: Introductionmentioning

confidence: 99%

Pleiotropic effects of pitavastatin

Davignon

2012

Brit J Clinical Pharma

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“…Hypercholesterolaemia is a known risk factor for cardiovascular disease, and statin therapy has led to a significant reduction in morbidity and mortality from adverse cardiac events, stroke, and peripheral arterial disease [140,141]. Statins block the enzyme necessary for the production of L-mevalonate, an intermediary product in cholesterol synthesis.…”

Section: Statinsmentioning

confidence: 99%

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sebastián¹,

Corral²,

Montañana³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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“…Some studies suggest that benefi ts of a treatment with statins may not be entirely due to their effects on LDL cholesterol. It is postulated that statins possess anti-infl ammatory, antioxidant, and antithrombotic activity (Liao , 2005 ;Ray et al , 2006 ;Sadowitz et al , 2010 ).…”

Section: Current Strategies For Lowering Cholesterol Level In Bloodmentioning

confidence: 99%

Squalene monooxygenase – a target for hypercholesterolemic therapy

Belter¹,

Skupińska²,

Giel-Pietraszuk

et al. 2011

BCHM

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Squalene monooxygenase catalyzes the epoxidation of C-C double bond of squalene to yield 2,3-oxidosqualene, the key step of sterol biosynthesis pathways in eukaryotes. Sterols are essential compounds of these organisms and squalene epoxidation is an important regulatory point in their synthesis. Squalene monooxygenase downregulation in vertebrates and fungi decreases synthesis of cholesterol and ergosterol, respectively, which makes squalene monooxygenase a potent and attractive target of hypercholesterolemia and antifungal therapies. Currently some fungal squalene monooxygenase inhibitors (terbinafi ne, naftifi ne, butenafi ne) are in clinical use, whereas mammalian enzymes ' inhibitors are still under investigation. Research on new squalene monooxygenase inhibitors is important due to the prevalence of hypercholesterolemia and the lack of both suffi cient and safe remedies. In this paper we (i) review data on activity and the structure of squalene monooxygenase, (ii) present its inhibitors, (iii) compare current strategies of lowering cholesterol level in blood with some of the most promising strategies, (iv) underline advantages of squalene monooxygenase as a target for hypercholesterolemia therapy, and (v) discuss safety concerns about hypercholesterolemia therapy based on inhibition of cellular cholesterol biosynthesis and potential usage of squalene monooxygenase inhibitors in clinical practice. After many years of use of statins there is some clinical evidence for their adverse effects and only partial effectiveness. Currently they are drugs of choice but are used with many restrictions, especially in case of children, elderly patients and women of childbearing potential. Certainly, for the next few years, statins will continue to be a suitable tool for cost-effective cardiovascular prevention; however research on new hypolipidemic drugs is highly desirable. We suggest that squalene monooxygenase inhibitors could become the hypocholesterolemic agents of the future.

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Basic Science Review Section: Statin Therapy—Part II: Clinical Considerations for Cardiovascular Disease

Cited by 21 publications

References 135 publications

Pleiotropic effects of pitavastatin

Pleiotropic effects of pitavastatin

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Squalene monooxygenase – a target for hypercholesterolemic therapy

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