1. 4S: Scandinavian Simvastatin Survival Study
Purpose
To determine whether simvastatin reduces morbidity and mortality in patients with high total cholesterol who have angina or previous myocardial infarction
Reference
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994:344:1383–9.

2. 4S: Scandinavian Simvastatin Survival Study - TRIAL DESIGN -
Multicenter, randomized, double-blind, placebo-controlled
Patients
4444 patients (3617 men, 827 women), aged 35–70 years, with angina pectoris or previous MI, and high total cholesterol (210–310 mg/dL, 5.5–8.0 mmol/L); patients with MI in previous 6 months or unstable angina excluded
Follow up and primary endpoint
Primary endpoint: all-cause mortality. Median 5.4 years follow up
Treatment
Placebo or simvastatin 20 mg each evening, increased or decreased as necessary to 40 or 10 mg each evening to achieve aim of serum total cholesterol 115–200 mg/dL (3.0–5.2 mmol/L )

3. 4S: Scandinavian Simvastatin Survival Study - RESULTS -
In simvastatin group, compared with placebo, significant reduction in:
All-cause mortality
Fatal coronary events
Combined endpoint of nonfatal or fatal coronary events
Myocardial revascularization procedures (11.3 vs. 17.2%, relative risk 0.63, P< )
No significant differences in noncardiovascular death, including death from cancer, trauma or suicide
With simvastatin, total and LDL cholesterol and triglycerides reduced by 25%, 35% and 10%, respectively; HDL cholesterol increased by 8%
Drug well tolerated (in both groups, 6% withdrawal rate due to adverse events)

4. 4S: Scandinavian Simvastatin Survival Study - RESULTS continued -
All-cause mortality
Proportion
1.00
alive
0.95
0.90
0.85
Placebo
Simvastatin
(RR = 0.7, P=0.0003)
0.80 1 2 3 4 5 6
Years after randomization
Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–89.

5. 4S: Scandinavian Simvastatin Survival Study - RESULTS continued -
Coronary events
Placebo
Simvastatin
Relative risk
n=2223
n=2221 P
(95% CI)
No. (%)
No. (%)
Fatal
Definite acute MI 63 30
Probably MI 5 5
All
189 (8.5)
111 (5.0)
0.58 (0.46–0.73)
Nonfatal* or fatal
622 (28)
431 (19)
0.66 (0.59–0.75)
<
* One or more nonfatal major
coronary events
Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–89.

6. 4S: Scandinavian Simvastatin Survival Study - RESULTS continued -
Causes of noncardiovascular death
Placebo
Simvastatin
(n=2223)
(n=2221)
Cancer
Suicide
Trauma
Other
Total 35 33 4 5 3 1 7 7
49 (2.2%)
46 (2.1%)
Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–89.

7. 4S: Scandinavian Simvastatin Survival Study - SUMMARY -
In patients with angina or previous MI and high total cholesterol, simvastatin reduced:
All-cause mortality
Fatal and nonfatal coronary events
Need for coronary artery bypass surgery or angioplasty