Statins effectiveness

Vasudevan AR, Hamirani YS, Jones PH. Safety of statins effects on muscle and the liver. Cleve ClinJ Med. 2005 72 990-993, 996-1001. 

Some studies have also suggested that CYP46A1 polymorphisms may be linked to AD [135-145]. As discussed previously, 24S-hydroxycholesterol is an important regulator of ApoE -mediated cholesterol transfer from astrocytes to glia and excess 24S-hydroxycholesterol may be neurotoxic and pro-inflammatory [100,111,146-148]. Reports regarding statin effects on 24S-hydroxycholesterol have been mixed. Some studies demonstrated decreases in 24S-hydroxycholesterol levels following statin treatment [90,149,... 

Much of the prior discussion has focused upon statin effects on cholesterol pathways. However, recent data suggest statin benefit in AD may occur via mechanisms completely independent of cholesterol lowering. For example, samples are known to modulate isoprenylation pathways and have potentially very potent anti-inflammatory activities [161]. Indeed, inhibition of proteins that are dependent upon isoprenylation, such as the Ras GT-Pase superfamily, has been suggested to be an import step in the inhibition of iNOS stimulated cytokine release [161]. In order to better understand... 

Vaughan CJ (2003) Prevention of stroke and dementia with statins effects beyond Upid lowering. Am J Cardiol 91 23B-29B... 

Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloflf R, et al (1999) f -Secretase cleavage of Alzheimer s amyloid precursor protein by transmembrane aspartic protease BACE. Science 286 735-741 Vaughan CJ (2003) Prevention of stroke and dementia with statins effects beyond lipid lowering. Am J Cardiol 9E23B-29B... 

Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond Hpid lowering-are they clinically relevant. Eur Heart J 2003 24 225-48. 

The phenyl group became a practical protective group for carboxylic acids when Sharpless published a mild, effective one-step method for its conversion to a carboxylic acid. It has recently been used in a synthesis of the amino acid statine, where it served as a masked or carboxylic acid equivalent. ... 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

HMG-CoA reductase inhibitors (statins). This effect has been suggested to account for some of the side effects of statins like myositis or rhabdomyolysis. 

Furthermore, there is some evidence for pleiotrophic effects (e.g., effects on hemostasis, vascular function, anti-inflammatory effects, and stabilizing effects on atherosclerotic plaques) of statins. The clinical relevance of this (and the potential difference between the various statins) is at present uncertain but subject to intense investigation. 

The effect of statins on plasma lipids and lipoproteins is rapidly seen and fully achieved after 4-6 weeks of treatment. The effect persists unchanged during continued use for several years, but after stopping the diug, LDL-cholesterol rapidly increases to pretreatment levels. Treatment with statins is therefore usually continued indefinitely and not as a short-term cure. Finally, it is generally advisable to use the statins that have documented their efficacy in clinical trials (evidence-based medicine). 

Abdominal symptoms including changes in bowel function, rash, and disturbances of sleep have been reported, but in general statins are remarkably free of side effects. Thus, in the large clinical trials comprising... 

The effect of a statin is usually determined by measuring fasting plasma lipids and lipoproteins after 4-6 weeks of treatment. Liver enzymes and eventually creatine kinase (in case of myositis liver enzymes are usually also elevated) are measured simultaneously to exclude side effects related to liver and muscles. After the treatment goal has been reached, blood sampling is usually performed 1-2 times a year. 

Ray KK, Cannon CP (2005) The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes. J Am Coll Cardiol 46 1425-1430... 

Rhabdomyolysis is disintegration and death of muscle cells (myocytes). It is an important but rare side effect of treatment with statins. 

Once has been determined in the absence of inhibitor, can be calculated from equation (47). K, values are used to compare different inhibitors of the same enzyme. The lower the value for K, the more effective the inhibitor. For example, the statin drugs that act as competitive inhibitors of HMG-CoA reductase (Chapter 26) have values several orders of magnimde lower than the AT for the substrate HMG-CoA. 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

Liao JK, Laufs U. Pleiotropic effects of statins. Anna Rev Pharmacol Toxicol 2005 45 89-118. 

Greisenegger S, MuUner M, Tentschert S, Lang W, Lalouschek W. Effect of pretreatment with statins on the severity of acute ischemic cerebrovascular events. J Neurol Sci 2004 221 5-10. 

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