A strategy to reduce cardiovascular disease by more than 80%.
OBJECTIVE
To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels.


METHODS
We quantified the efficacy and adverse effects of the proposed formulation from published meta-analyses of randomised trials and cohort studies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin.


METHODS
Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalence of adverse effects.


RESULTS
The formulation which met our objectives was: a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg)); three blood pressure lowering drugs (for example, a thiazide, a beta blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose; folic acid (0.8 mg); and aspirin (75 mg). We estimate that the combination (which we call the Polypill) reduces IHD events by 88% (95% confidence interval 84% to 91%) and stroke by 80% (71% to 87%). One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomised trials shows that the Polypill would cause symptoms in 8-15% of people (depending on the precise formulation).


CONCLUSIONS
The Polypill strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.
Wald
N J
NJ
Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London EC1M 6BQ. n.j.wald@qmul.ac.uk
Law
M R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*
D000959:Antihypertensive Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D005492:Folic Acid; D001241:Aspirin