Authors
Scandinavian Simvastatin Survival Study group
Title
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease
References
Lancet. 1994 Nov 19;344(8934):1383-9.
Background
High serum cholesterol has been viewed as the main cause of coronary atherosclerosis. Several cholesterol lowering interventions have reduced coronary heart disease (CHD) events in primary and secondary prevention trials. No trial to this point has demonstrated cholesterol lowering has mortality benefit.
Purpose
To test the hypothesis that lowering cholesterol with simvastatin would improve survival of patients with CHD.
Design
  • Randomized, double-blind, placebo-controlled trial
  • 4444 men and women aged 35-70 years with history of angina or myocardial infarction
  • Serum cholesterol 5.5-8.0 mmol/L
Exclusion Criteria
  • Premenopausal women
  • Secondary hypercholesterolemia
  • Prinzmetal angina
  • Planned CABG or angioplasty or MI during preceding 6 months
  • CHF requiring medical treatment
  • Atrial fibrillation, cardiomegaly, valvular heart disease, stroke
  • Hepatic dysfunction or drug/alcohol abuse
Follow-Up
Median 5.4 years
Treatment Regimen
  • Simvastatin (dose titrated based on serum cholesterol at 6 and 18 weeks) vs. placebo
  • Clinic visits every 6 weeks for the first 18 months and then 6 months thereafter. Measurement of lipids and routine haematology/urine evaluation at each visit.
Results

Primary Endpoints

  • Total mortality: simvastatin (8%) vs. placebo (12%) – RR 0.70 (95% CI 0.58-0.85, p=0.0003)

Secondary Outcomes

  • Major coronary events (coronary death or non-fatal MI, resuscitated cardiac arrest)
  • Combined secondary endpoint: 0.66 (95% CI 0.59-0.75, p<0.0001) in simvastatin group
  • Coronary death: 0.58 (95% CI 0.46-0.73) in simvastatin group
Summary
Long term treatment with simvastatin is safe and improves survival in patients with established CHD.