The Heart Protection Study ( HPS ), a large, multicenter, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients, including 5,963 patients with type 2 diabetes ( 2,978 on Simvastatin and 2,985 on placebo ) showed that Simvastatin 40 mg/day significantly reduced total and coronary heart disease ( CHD ) mortality; non-fatal myocardial infarction, stroke, and revascularization procedures ( coronary and non-coronary ).
Participants in HPS ( mean age 64 ) were at high risk of developing a major coronary event because of existing CHD ( 65% ), diabetes ( type 2, 26%; type 1, 3% ), history of stroke or other cerebrovascular disease ( 16% ), peripheral vessel disease ( 33% ), or hypertension in males greater than 65 years ( 6% ).
Treatment with Simvastatin has produced significant relative risk reductions for all components of the two composite endpoints, including major coronary events comprised of CHD mortality and non-fatal myocardial infarction, and major vascular events comprised of stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures ( 27% for major coronary events and 24% for major vascular events, p less than 0.0001 ).
Diabetic patients showed risk reductions for MCE and MVE ( 27% and 22%, respectively; p less than 0.0001 ) due to Simvastatin treatment regardless of baseline A1C levels or obesity with the greatest effects seen for diabetic patients without CHD.
The Scandinavian Simvastatin Survival Study ( 4S ) assessed the effect of therapy with Simvastatin on total mortality in 4,444 patients with CHD and baseline total cholesterol 212-309 mg/dL ( 5.5-8.0 mmol/L ). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either Simvastatin 20-40 mg/day ( n=2,221 ) or placebo ( n=2,223 ) for a median duration of 5.4 years.
In 4S, treatment with Simvastatin significantly reduced the risk of mortality by 30% ( p=0.0003 ), and the risk of CHD mortality by 42% ( p=0.00001 ). Simvastatin also significantly decreased the risk of major coronary events ( CHD mortality plus hospital-verified and silent non-fatal myocardial infarction ) by 34% ( p less than 0.00001 ), and the risk of fatal plus non-fatal cerebrovascular events ( combined stroke and transient ischemic attacks ) by 28% ( p=0.033 ).
Simvastatin has been shown to be effective in reducing total cholesterol, low-density lipoprotein cholesterol ( LDL-C ) in heterozygous familial and non-familial forms of hyperlipidemia and in mixed hyperlipidemia. Maximal to near maximal response is generally achieved within 4-6 weeks and maintained during chronic therapy. Simvastatin consistently and significantly decreased total cholesterol, LDL C, total C/HDL C ratio, and LDL C/HDL C ratio; Simvastatin also decreased triglycerides and increased high-density lipoprotein cholesterol ( HDL-C ). ( Xagena )
Source: Merck, 2011