Cardiovascular outcome trial · Lancet 1994
4S trial
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
The bottom line
In patients with coronary heart disease and elevated cholesterol, simvastatin reduced the risk of death and major coronary events compared with placebo over about 5.4 years.
BenefitUS status: US-approved
At a glance
- Medicine
- Simvastatin
- Compared with
- Placebo
- People
- 4,444
- Who took part
- Patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet
- Design
- Randomised, double-blind, placebo-controlled trial
- Follow-up
- 5.4 years median follow-up
- Main question
- All-cause mortality
Main result
The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively.
Effect on LDL cholesterol
-35% LDL cholesterol (total cholesterol -25%, HDL cholesterol +8%)
Other results
There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures.
Safety
Simvastatin produced the above lipid changes with few adverse effects; long-term treatment with simvastatin is safe.
In the trial's own words
“256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003).”
Quoted from the abstract of Lancet 1994, checked word for word against PubMed. PubMed 7968073
How this medicine works, where it stands and what it costs: Statins
Common questions
What did the 4S trial find?
In patients with coronary heart disease and elevated cholesterol, simvastatin reduced the risk of death and major coronary events compared with placebo over about 5.4 years.
Who was in 4S?
4,444 people. Patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet.
What was 4S's main result?
The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively.
How much did LDL cholesterol change in 4S?
-35% LDL cholesterol (total cholesterol -25%, HDL cholesterol +8%)
Related trials
- WOSCOPS (1995)In middle-aged men with moderate hypercholesterolemia and no prior MI, pravastatin significantly reduced coronary events and cardiovascular death without increasing noncardiovascular deaths.
- CARE (1996)In patients with average cholesterol levels after myocardial infarction, pravastatin significantly reduced the risk of fatal coronary events and nonfatal MI, as well as the need for revascularization and stroke, without a significant effect on overall mortality.
- AFCAPS/TexCAPS (1998)In men and women with average cholesterol but low HDL-C and no known heart disease, lovastatin substantially lowered the risk of a first major coronary event.
- LIPID (1998)In patients with coronary heart disease and a broad range of cholesterol levels, pravastatin reduced death from coronary heart disease, overall mortality, and other cardiovascular events compared with placebo.
Get your LDL treated to a goal
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