Authors
Heart Protection Study Collaborative Group
Title
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high risk individuals
References
Lancet. 2002 Jul 6;360(9326):7-22.
Background
Observational studies in different populations indicate a continuous positive relationship between coronary heart disease risk and blood LDL cholesterol concentration. There is not clear threshold below which a lower concentration is not associated with lower risk.
Purpose
To determine the long term effects of cholesterol lowering therapy on vascular and non-vascular mortality and major morbidity.
Design
  • Randomized, double-blind, placebo-controlled trial (2x2 design with antioxidant vitamins)
  • 20,536 patients between 40-80 years with non-fasting total cholesterol of at least 3.5mmol/L
  • Must have substantial 5 year risk of cardiovascular death (i.e. previous documented CAD, CVD, PVD or DM 1 or 2)
  • receiving a diuretic and ACE inhibitor (other vasodilators permitted if intolerant to ACE inhibitor), could be receiving digoxin
Exclusion Criteria
  • If patient's physician felt statin therapy was clearly indicated already
  • Chronic liver disease or abnormal liver function tests
  • Evidence of inflammatory muscle disease (i.e. polymyositis)
  • Serum creatinine ≥200 umol/L, reversible obstructive lung disease
  • Concurrent treatment with fibrates, niacin or cyclosporine
  • Severe heart failure or other life threatening conditions
Follow-Up
Mean 5.3 years
Treatment Regimen
  • Simvastatin 40 mg vs. placebo
  • Clinic follow up at 4, 8, 12 months and then 6 monthly until study completion. Compliance, lipids and routine haematology assessed at each visit
Results

Primary Endpoints

  • Death from all causes: 12.9% (simvastatin) vs. 14.7% (placebo); p<0.0003
  • Death from coronary heart disease: 5.7% (simvastatin) vs. 6.9% (placebo); p=0.0005
  • Death from all other causes: 5.3% (simvastatin) vs. 5.6% (placebo); p=0.4

Secondary Outcomes

(see study for complete list)

  • Reduction in coronary or non-coronary revascularization: 9.1% (simvastatin) vs. 11.7% (placebo); p<0.0001
  • Reduction in non-fatal MI or coronary death: 8.7% (simvastatin) vs. 11.8% (placebo); p<0.0001
  • Reduction in fatal or non-fatal strokes: 4.3% (simvastatin) vs. 5.7% (placebo); p<0.0001
Summary
  • The addition of simvastatin 40 mg to existing treatments safely produces substantial additional benefits (reduction in total mortality, CHD mortality and MI/stroke) for a wide range of high-risk patients irrespective of their initial cholesterol concentrations.
  • Allocation to 40 mg simvastatin daily reduced the rates of myocardial infarction of stroke, and of revascularization by about 25%. Accounting for non-compliance, 5 years of simvastatin use would prevent about 70-100 people per 1000 from suffering at least one of the major vascular events. The size of the 5-year benefit depends mainly on the individual's