Reduction of Cardiovascular Events by Simvastatin in Nondiabetic Coronary Heart Disease Patients With and Without the Metabolic Syndrome: Subgroup analyses of the Scandinavian Simvastatin Survival Study (4S)

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To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III).


Subgroup analyses were performed on data from 3,933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5-8.0 mmol/l, and serum triglyceride level ≤2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S), a randomized, placebo-controlled trial. End points were total mortality, coronary mortality, major CHD event, myocardial revascularization, any CHD event, stroke, and any atherosclerotic event.


Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3,040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36-0.82), coronary mortality 0.39 (0.23-0.65), major CHD event 0.59 (0.45-0.77), and any atherosclerotic event 0.69 (0.56-0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56-0.91), 0.62 (0.45-0.84), 0.71 (0.61-0.82), and 0.76 (0.68-0.85).


Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.

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