Scandinavian Simvastatin Survival Study

The Scandinavian Simvastatin Survival Study (also known under the abbreviation 4S) is a multicenter clinical trial that was performed in the 1990s in Scandinavia.

The objective of the study was to assess effect of a cholesterol-lowering drug called simvastatin on mortality and morbidity in a group of 4444 patients with coronary heart disease, ages between 35 and 70 years. The patients exhibited moderate hypercholesterolemia, between 5.5 and 8.0 mmol/l. The trial showed that treatment of patients suffering from coronary heart disease with simvastatin had a lowering effect on mortality and morbidity.

2223 patients were assigned placebo and 2221 were assigned simvastatin treatment for a mean period of 5.4 years. There was a 30% relative reduction in the risk of death with simvastatin treatment. The absolute coronary-heart-disease mortality was reduced from 8.5% to 5.0%, making the number needed to treat around 30 (30 patients would need to be treated to prevent one death). Additionally there was no excess morbidity of non-cardiac deaths from causes like cancer or suicide, a concern that has occasionally arisen in respect to statins.

The treatment of 100 patients for six years would prevent four deaths of the disease and seven non-fatal myocardial infarcts.

The 4S study turned out to be a milestone in cardiology and evidence-based medicine — it was clearly proven that treatment with statins changed the occurrence of events of patients with coronary heart disease.

A host of other large multicenter clinical trials followed that paved the way to widespread use of this class of pharmaceuticals.

References

• The Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389 PMID 7968073
• The Scandinavian Simvastatin Survival Study Group. Design and baseline results of the Scandinavian Simvastatin Survival Study of patients with stable angina and/or previous myocardial infarction. Am J Cardiol 1993;71:393-400 PMID 8430625
• Pedersen, T.R., L.Wilhelmsen, O.Faergeman, et al.: Follow-up study of patients randomized in the Scandinavian Simvastatin Survival Study (4S) of cholesterol lowering. Am J Cardiol 2000;86:257-262 PMID 10922429