Simvastatin cholesterol-lowering effects

Nordin C, Dahl ML, Eriksson M, Sjoberg S (1997) Is the cholesterol-lowering effect of simvastatin influenced by CYP2D6 polymorphism Lancet 350 29-30... 

In an isolated case, phenytoin reduced the cholesterol-lowering effect of simvastatin, fluvastatin and atorvastatin. The concurrent use of phenytoin and fluvastatin modestly raises the levels of both drugs. 

Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004 363 757-67. 

Recent reports on clinical trials of pravastatin and simvastatin have shown a significant reduction in patient mortality rates for both hypercholesterolemic patients without known coronary heart disease and for those with existing coronary heart disease [7,8], These trials have established cholesterol-lowering agents as an effective treatment for coronary disease and have stimulated the search for new cholesterol-lowering agents with other mechanisms of action. 

Clarke R, Lewington S, Youngman L et al. (2002). Underestimation of the importance of blood pressure and cholesterol for coronary heart disease mortality in old age. European Heart Journal 23 286-293 Collins R, Armitage J, Parish S et al. (2004). Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high-risk conditions. Lancet 363 757-767 Dahlof B, Devereux RB, Kjeldsen SE et al. (2002). Cardiovascular morbidity and mortality in Losartan Intervention For End Point Reduction in Hypertension (LIFE) study a randomized trial against atenolol. Lancet 359 995-1003... 

The Health Service reforms in the United Kingdom in 1991 avoided this trap and used instead the cost-utility concept. Cost-effectiveness takes into account only the cost of a single standardized outcome cost-utility looks at the costs of a range of different outcomes, such as extra years of survival and improved quality of life. A Dutch study of two cholesterol-lowering drugs, for example, showed that cholestyramine cost 131,000 Dutch Guilders per year of life saved compared with simvastatin which cost 31,500 Dutch Guilders. ... 

Over the last decade, several studies in tens of thousands of patients have revealed that lowering cholesterol, specifically lowering LDL cholesterol with statins, is effective for both primary and secondary prevention of IHD-related events. Statins shown to decrease morbidity and mortality associated with IHD include lovastatin, simvastatin, pravastatin, and atorvas-tatin.22,23 A recent meta-analysis showed that the risk of major adverse cardiac events is reduced by 21% with the use of statins in patients at high risk for IHD-related events.23... 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

The adverse effects of statins have been reviewed in the light of the ever increasing dosages that are being used to lower LDL cholesterol to a minimum (2). In another review high doses of atorvastatin and simvastatin were specially emphasized (3). 

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