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 diseaseThis 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 controlledRandomized, double-blind, placebo controlled 6595 men, 45 to 64 years of age6595 men, 45 to 64 years of age Average follow-up of 4.9 years (seen at 3 month intervals)Average follow-up of 4.9 years (seen at 3 month intervals) Pravastatin (40 mg each evening) vs. placeboPravastatin (40 mg each evening) vs. placebo James Shepherd, et al, N Engl J Med 1995;333:1301-7

WOS Baseline Characteristics Mean lipid levels:Mean lipid levels: –TC = 272 mg/dL –LDL = 192 mg/dL –HDL = 44 mg/dL –Trigs = mg/dL 5% of patients with angina5% of patients with angina 3% of patients with claudication3% of patients with claudication 8% of patients with abnormal EKG8% of patients with abnormal EKG 44% current smokers, 34% ex-smokers44% 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 %1 risk factor:100 % 2 risk factors:44+ %2 risk factors:44+ % 3 risk factors:?3 risk factors:? Family history:?Family history:? Current CHD:5+ %?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 Non-fatal MI or coronary heart disease death as a first eventSecondary Non-fatal MINon-fatal MI Coronary heart disease deathCoronary heart disease death James Shepherd, et al, N Engl J Med 1995;333:1301-7

Other Endpoints Cardiovascular mortalityCardiovascular mortality Total mortalityTotal mortality Coronary revascularization proceduresCoronary revascularization procedures James Shepherd, et al, N Engl J Med 1995;333:1301-7

WOS Reduction in Lipids Pravastatin reduced lipid levels by*: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: pravastatin (intention-to-treat) pravastatin (actual treatment) placebo (actual treatment) placebo (intention -to-treat)

Nonfatal MI or CHD Death (Primary Endpoint) 31%RiskReduction P= James Shepherd, et al, N Engl J Med 1995;333:1301-7

Non-Fatal MI (Secondary Endpoint) 31%RiskReduction P= 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%RiskReduction P=0.033 James Shepherd, et al, N Engl J Med 1995;333:1301-7

Coronary Interventions Intervention PlaceboPravastatin Risk (n= 3293)(n=3302) Reductions p-value (n= 3293)(n=3302) Reductions p-valueCoronary Angiography % PTCA / CABG % James Shepherd, et al, N Engl J Med 1995;333:1301-7

Total Mortality P= %RiskReduction 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.”“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 angiograms14 coronary angiograms 8 revascularization procedures8 revascularization procedures And avoid: 20 nonfatal MIs20 nonfatal MIs 7 CHD deaths7 CHD deaths 2 additional deaths2 additional deaths James Shepherd, et al, N Engl J Med 1995;333:1301-7