Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
James Shepherd, M.D., Stuart M. Cobbe, M.D., Ian Ford, Ph.D., Christopher G. Isles., M.D., A. Ross Lorimer, M.D., Peter W. Macfarlane, Ph. D., James H. McKillop, M.D., and Christopher J. Packard, D. Sc., for the West of Scotland Coronary Prevention Study Group
N Engl J Med 1995;333:1301-7
Background
This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease
James Shepherd, et al, N Engl J Med 1995;333:1301-7
West of Scotland Coronary Prevention Study Group (WOS)
Randomized, double-blind, placebo controlled
6595 men, 45 to 64 years of age
Average follow-up of 4.9 years (seen at 3 month intervals)
Pravastatin (40 mg each evening) vs. placebo
James Shepherd, et al, N Engl J Med 1995;333:1301-7
WOS Baseline Characteristics
Mean lipid levels:
TC = 272 mg/dL
LDL = 192 mg/dL
HDL = 44 mg/dL
Trigs = 162-164 mg/dL
5% of patients with angina
3% of patients with claudication
8% of patients with abnormal EKG
44% current smokers, 34% ex-smokers
James Shepherd, et al, N Engl J Med 1995;333:1301-7
WOSCOPS: High Risk Primary Prevention
Risk Factors...
1 risk factor: 100 %
2 risk factors: 44+ %
3 risk factors: ?
Family history: ?
Current CHD: 5+ %?
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Endpoints
Primary
Non-fatal MI or coronary heart disease death as a first event
Secondary
Non-fatal MI
Coronary heart disease death
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Other Endpoints
Cardiovascular mortality
Total mortality
Coronary revascularization procedures
James Shepherd, et al, N Engl J Med 1995;333:1301-7
WOS Reduction in Lipids
Pravastatin reduced lipid levels by*:
20% reduction in TC
26% reduction in LDL
12% reduction in Trigs
5% increase in HDL
*Data analyzed according to the treatment actually received not according to the intention-to-treat principle
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Effects of Pravastatin Therapy on Plasma LDL Cholesterol Levels
James Shepherd, et al, N Engl J Med 1995;333:1301-7
pravastatin (intention-to-treat)
pravastatin (actual treatment)
placebo (actual treatment)
placebo (intention -to-treat)
Nonfatal MI or CHD Death (Primary Endpoint)
31%
Risk
Reduction
P=0.0001
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Non-Fatal MI (Secondary Endpoint)
31%
Risk
Reduction
P=0.0005
James Shepherd, et al, N Engl J Med 1995;333:1301-7
CHD Death (Secondary Endpoint)
28%
Risk
Reduction
P=0.13
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Cardiovascular Death
32%
Risk
Reduction
P=0.033
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Coronary Interventions
Intervention Placebo Pravastatin Risk
(n= 3293) (n=3302) Reductions p-value
Coronary
Angiography 128 90 31% 0.007
PTCA / CABG 80 51 37% 0.009
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Total Mortality
P=0.051
22%
Risk
Reduction
James Shepherd, et al, N Engl J Med 1995;333:1301-7
WOS Results/Clinical Events
James Shepherd, et al, N Engl J Med 1995;333:1301-7
WOS Conclusions
“Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.”
James Shepherd, et al, N Engl J Med 1995;333:1301-7
Projected Benefits
Treatment of 1000 hypercholesterolemic middle aged
men with pravastatin for five years will avoid:
14 coronary angiograms
8 revascularization procedures
And avoid:
20 nonfatal MIs
7 CHD deaths
2 additional deaths
James Shepherd, et al, N Engl J Med 1995;333:1301-7