Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S)

Am J Cardiol. 1995 Sep 28;76(9):64C-68C. doi: 10.1016/s0002-9149(99)80473-1.


The Scandinavian Simvastatin Survival Study (4S) was designed to evaluate the effects of cholesterol reduction with simvastatin on mortality and morbidity in patients with coronary artery disease (CAD). A total of 4,444 patients with angina pectoris or previous myocardial infarction and serum cholesterol levels of 213-310 mg/dl (5.5-8.0 mmol/liter) while treated with a lipid-lowering diet were randomly assigned to double-blind treatment with simvastatin or placebo. Over the 5.4 years of median follow-up, simvastatin produced changes in total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol of -25%, -35%, and +8%, respectively, with minimal adverse effects. A total of 256 patients (12%) in the placebo group died compared with 182 (8%) in the simvastatin group, a risk reduction of 30% (p = 0.0003) attributable to a 42% reduction in the risk of coronary death. Noncardiovascular causes accounted for 49 and 46 deaths in the placebo and simvastatin groups, respectively. Major coronary events were experienced by 622 patients (28%) in the placebo group and 431 patients (19%) in the simvastatin group, corresponding to a risk reduction of 34% (p < 0.00001). This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged > or = 60 years. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularization procedures. Simvastatin was beneficial regardless of whether patients had a history of myocardial infarction or whether they were smokers or had hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control
  • Double-Blind Method
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lovastatin / analogs & derivatives*
  • Lovastatin / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Risk Factors
  • Scandinavian and Nordic Countries
  • Sex Factors
  • Simvastatin
  • Survival Rate


  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lovastatin
  • Simvastatin