4S: Scandinavian Simvastatin Survival Study

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 199434413839.

2
4S Scandinavian Simvastatin Survival Study-
TRIAL DESIGN -

• Design
• Multicenter, randomized, double-blind,
  placebo-controlled
• Patients
• 4444 patients (3617 men, 827 women), aged 3570
  years, with angina pectoris or previous MI, and
  high total cholesterol (210310 mg/dL, 5.58.0
  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 115200 mg/dL (3.05.2 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, Plt0.00001)
• 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
0.80
0
0
1
2
3
4
5
6
Years after randomization
Scandinavian Simvastatin Survival Study Group.
Lancet 1994344138389.

5
4S Scandinavian Simvastatin Survival Study-
RESULTS continued -

Coronary events
Placebo
Simvastatin
Relative risk
P
n2223
n2221
(95 CI)
No. ()
No. ()
Fatal
Definite acute MI
63
30

Probably MI
5
5
All
189 (8.5)
111 (5.0)
0.58 (0.460.73)


Nonfatal or fatal
622 (28)
431 (19)
0.66 (0.590.75)
lt0.00001
One or more nonfatal major coronary events
Scandinavian Simvastatin Survival Study Group.
Lancet 1994344138389.
6
4S Scandinavian Simvastatin Survival Study-
RESULTS continued -

Causes of noncardiovascular death
Placebo
Simvastatin
(n2223)
(n2221)
35
33
4
5
3
1
7
7
49 (2.2)
46 (2.1)
Scandinavian Simvastatin Survival Study Group.
Lancet 1994344138389.
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