Scandinavian Simvastatin Survival Study Group - 4S


Simvastatin vs placebo for mortality in coronary heart disease


Will simvastatin result in improved survival of patients with coronary heart disease?

Study Design

Study Design:

Patients Enrolled: 4444
Mean Follow Up: 4.9-6.3 years (median 5.4 years)
Mean Patient Age: 35-70
Female: 19%

Patient Populations:

Patients 35–70 years of age with angina pectoris or previous MI (≥6 months earlier) and serum cholesterol 5.5–8.0 mmol/L (mean LDL 188 mg/dL).


Unstable angina, secondary hypercholesterolemia, premenopausal women, planned coronary artery bypass surgery, congestive heart failure or angioplasty.

Primary Endpoints:

all-cause mortality

Secondary Endpoints:

serum lipid levels, major coronary events

Drug/Procedures Used:

Simvastatin 20–40 mg (dose increased from 20 to 40 mg/day if target range of 3.0-5.2 mmol/L not achieved) once daily or placebo.

Principal Findings:

Simvastatin patients had a significant 30% relative risk reduction in overall mortality (8.2% vs. 11.5%; p = 0.0003), as well as 39% fewer nonfatal MIs (7.4% vs. 12.1%), 41% fewer ischemic heart disease deaths (5.0% vs. 8.5%), and 34% fewer myocardial revascularization procedures (11.3% vs. 17.2%). There was no difference between the 2 groups in the incidence of noncardiovascular deaths. Simvastatin therapy was associated with 25% lower total cholesterol(TC), 35% lower LDL, and 8% higher HDL levels. Simvastatin reduced the risk of major coronary events in ALL quartiles of baseline lipid lipid levels, including a 35% risk reduction among patients in the lowest quartile of baseline LDL. The overall rates of adverse effects were similar in the two groups. A subsequent cost analysis showed that simvastatin-treated patients had 34% fewer cardiovascular-related hospital days and that there was $3,872 savings/patient, reducing the effective drug cost by 88% to 28 cents/day (see Circulation 1996;93:1796). Other analyses have shown that women, the elderly (>65 years old), and diabetics all had significant reductions in major events (see references below).


Long-term treatment with simvastatin is safe and results in a significant reduction in all-cause mortality and coronary events in patients with coronary heart disease and baseline elevated serum cholesterol levels.


Lancet 1994;344:1383–1389. Primary report. Circulation 1996;93:1796 and N Engl J Med 1997; 336: 332-6. Cost effectiveness analyses. Circulation 1997;96:4211-18.Women and elderly analysis. Ann Intern Med 1999;59:2661-67. Diabetes analysis.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease

Keywords: Cholesterol, Coronary Artery Disease, Risk Reduction Behavior, Myocardial Revascularization, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Drug Costs, Diabetes Mellitus

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