Management of Dyslipidaemias
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- Hvizdos, K.M. & Goa, K.L. Dis-Manage-Health-Outcomes (2000) 7: 83. doi:10.2165/00115677-200007020-00004
Dyslipidaemias are major modifiable risk factors for the development of atherosclerosis and its sequelae, namely coronary heart disease (CHD) and peripheral vascular disease. CHD is the leading cause of morbidity and mortality in men and women in Western countries; the costs associated with this disease are substantial and place a large burden on society.
The goal of therapy in patients with dyslipidaemia is to achieve target serum lipid levels (established by treatment guidelines) in an effort to reduce the risk of asymptomatic individuals developing CHD (primary prevention) or to slow or retard the progression of atherosclerosis in patients with established CHD (secondary prevention). A multifactorial approach including lifestyle modifications and, if necessary, pharmacological intervention is recommended.
Simvastatin is a competitive and reversible inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase. It causes marked reductions in serum low density lipoprotein cholesterol (LDL-C) levels and reductions in serum triglyceride levels in patients with hypertriglyceridaemia. Simvastatin also increases serum high density lipoprotein cholesterol (HDL-C) levels and is the first HMG-CoA reductase inhibitor indicated for this use.
The Scandinavian Simvastatin Survival Study (4S) established that simvastatin 20 to 40 mg/day reduces total mortality (by 30% at 5 years compared with placebo) in patients with CHD, mostly because of a reduction in cardiovascular mortality (42% reduction at 5 years). This reduction in mortality was maintained for at least 8 years in simvastatin-treated patients in 4S. As secondary prevention simvastatin is cost effective in men, women and diabetic patients with CHD as shown by data from 4S. Available evidence also indicates that simvastatin slows the progression of coronary atherosclerosis. In patients with diabetes and CHD, 5-years’ treatment with simvastatin during 4S reduced the risk of coronary death and nonfatal myocardial infarction by 55% compared with a 32% reduction in nondiabetic patients with CHD. In high risk patients with CHD, other cardiovascular risk factors and dyslipidaemia, simvastatin 40 to 80 mg/day effectively reduced serum LDL-C and triglyceride levels and raised HDL-C levels.
The most common adverse events associated with simvastatin in clinical trials of 5 to 10 years’ duration were gastrointestinal upset and headache. These events were similar in incidence to that with placebo and did not necessitate a discontinuation of therapy. Asymptomatic elevations in hepatic transaminase levels and, rarely, myopathy have been described during simvastatin treatment.
Conclusions: The efficacy and tolerability of simvastatin at doses of up 80 mg/day are well established. Together with favourable effects on serum lipoprotein levels compared with related compounds and, more importantly, beneficial long term effects on morbidity and mortality in patients with CHD, simvastatin is firmly established as a first-line agent when cholesterol-altering pharmacotherapy is indicated for treatment of dyslipidaemia.