A strategy to reduce cardiovascular disease by more than 80%

doi:10.1136/bmj.326.7404.1419

BMJ 2003;326:1419 (28 June), doi:10.1136/bmj.326.7404.1419

Paper

A strategy to reduce cardiovascular disease by more than 80%

N J Wald, professor¹, M R Law, professor¹

¹ 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

Correspondence to: N J Wald n.j.wald{at}qmul.ac.uk

Objectives To determine the combination of drugs and vitamins,and their doses, for use in a single daily pill to achievea large effect in preventing cardiovascular disease with minimaladverse effects. The strategy was to simultaneously reducefour cardiovascular risk factors (low density lipoprotein cholesterol,blood pressure, serum homocysteine, and platelet function)regardless of pretreatment levels.

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

Outcome measures Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalenceof 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 enzymeinhibitor), each at half standard dose; folic acid (0.8 mg);and aspirin (75 mg). We estimate that the combination (whichwe call the Polypill) reduces IHD events by 88% (95% confidenceinterval 84% to 91%) and stroke by 80% (71% to 87%). One thirdof people taking this pill from age 55 would benefit, gainingon average about 11 years of life free from an IHD event orstroke. Summing the adverse effects of the components observedin randomised trials shows that the Polypill would cause symptomsin 8-15% of people (depending on the precise formulation).

Conclusion The Polypill strategy could largely prevent heartattacks and stroke if taken by everyone aged 55 and older andeveryone with existing cardiovascular disease. It would beacceptably safe and with widespread use would have a greaterimpact on the prevention of disease in the Western world thanany other single intervention.

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Whose Life Is It Anyway? The Polypill May Increase Health Inequalities: Michael A Soljak
bmj.com, 27 Jun 2003 [Full text]
Shabby Medical Thinking: Nicholas M Regush
bmj.com, 27 Jun 2003 [Full text]
A gauntlet thrown at drug companies or doctors?: Richard G Fiddian-Green
bmj.com, 28 Jun 2003 [Full text]
The 'Vacca Foeda' PolyPill: Joseph .C. Obi
bmj.com, 28 Jun 2003 [Full text]
Impact of single normal dose blood pressure medications: Bala Subramanian
bmj.com, 28 Jun 2003 [Full text]
Polypill drawbacks and multivitamin as alternative: BIll Sardi
bmj.com, 28 Jun 2003 [Full text]
The Big Issue: Dan Rutherford
bmj.com, 28 Jun 2003 [Full text]
new paradigm: Martin R Innes
bmj.com, 28 Jun 2003 [Full text]
Dumbfounded: Peter J Hosein
bmj.com, 28 Jun 2003 [Full text]
Also dumbfounded: Margaret J Tyson
bmj.com, 29 Jun 2003 [Full text]
Can anyone afford to live a very long life?: Mark Hochhauser, Ph.D.
bmj.com, 29 Jun 2003 [Full text]
A Sad Day For British Medicine: Allan Withnell
bmj.com, 29 Jun 2003 [Full text]
Treat people not populations: Eugene A. Rybinski
bmj.com, 29 Jun 2003 [Full text]
polypill ; for all races, sexes and seasons ?: Adesuyi Ajayi, et al.
bmj.com, 29 Jun 2003 [Full text]
Old joke and current practice: Adrian K Midgley
bmj.com, 29 Jun 2003 [Full text]
What do we die then?: Roger Wanner
bmj.com, 29 Jun 2003 [Full text]
POLYPILL, AN IDEA, PERHAPS A VERY GOOD ONE, BUT NOT A JOKE: CELIO LEVYMAN,MD,MSc, et al.
bmj.com, 30 Jun 2003 [Full text]
WHEN?: Linda L Gimnich
bmj.com, 30 Jun 2003 [Full text]
About as believable as the tooth fairy: Adam Jacobs
bmj.com, 30 Jun 2003 [Full text]
A pill a day keeps health away?: Ewan Hamnett
bmj.com, 30 Jun 2003 [Full text]
Shame on you BMJ!!: Michael C Bunbury, et al.
bmj.com, 30 Jun 2003 [Full text]
Nearer 66% rather than 88% IHD risk reduction after 2 years?: Eric S. Kilpatrick
bmj.com, 30 Jun 2003 [Full text]
Relative risks and meta-analysis: J Michael Henk
bmj.com, 30 Jun 2003 [Full text]
Unbelievable and unachievable: Mark J Garton
bmj.com, 30 Jun 2003 [Full text]
Multiple Polypill Benefits: Gerard T O'Brien
bmj.com, 1 Jul 2003 [Full text]
WHO should convene an aspirin meeting?: Gareth P Morgan
bmj.com, 1 Jul 2003 [Full text]
POLYPILL AGAIN,BUT IN THE THIRD WORLD: CELIO LEVYMAN,MD,MSc
bmj.com, 2 Jul 2003 [Full text]
Patients before populations: Peter N Trewby, et al.
bmj.com, 2 Jul 2003 [Full text]
Polypill treatment and the physical properties of blood.: Leslie.O. Simpson
bmj.com, 2 Jul 2003 [Full text]
Re: Shame on you BMJ!!: Daniel Weyandt
bmj.com, 2 Jul 2003 [Full text]
Reality check: Mike Schachter
bmj.com, 2 Jul 2003 [Full text]
Brave New World: Joachim P Sturmberg
bmj.com, 2 Jul 2003 [Full text]
Polypill Choices: Shah M Tauzeeh
bmj.com, 2 Jul 2003 [Full text]
Concept is correct: Paul W Masters
bmj.com, 2 Jul 2003 [Full text]
Logical consequence of current polypharmacy: Dr. Matthew L Grove
bmj.com, 2 Jul 2003 [Full text]
What must be done now.: William Plummer
bmj.com, 2 Jul 2003 [Full text]
Aspastatapril vs Polypill: Ketan K Dhatariya
bmj.com, 2 Jul 2003 [Full text]
Compliance with the Polypill: Anita Sainsbury
bmj.com, 3 Jul 2003 [Full text]
Re: What must be done now - correction.: William Plummer
bmj.com, 3 Jul 2003 [Full text]
Is The Paper a Spoof?: David A Brodie
bmj.com, 3 Jul 2003 [Full text]
Dubious mathematical assumptions: David M Reith
bmj.com, 3 Jul 2003 [Full text]
Total Mortality: Jeffrey R Johnstone
bmj.com, 4 Jul 2003 [Full text]
Modelling and assumptions need clarification: Tom Fahey, et al.
bmj.com, 5 Jul 2003 [Full text]
Polypill Debate: Stephen J Redmond
bmj.com, 5 Jul 2003 [Full text]
Cat amonsgt the pigeons: Adam L Brown
bmj.com, 5 Jul 2003 [Full text]
Eradicating cardiovascular disease with polypharmarcy: Dream or reality ?: Peter Marckmann
bmj.com, 6 Jul 2003 [Full text]
Willing suspense of disbelief: Elved B Roberts
bmj.com, 7 Jul 2003 [Full text]
'Magic pill' approach would shift focus from proven and cost-effective CVD prevention: Derek Yach, et al.
bmj.com, 7 Jul 2003 [Full text]
Salicylate deficiency: Gareth P Morgan
bmj.com, 7 Jul 2003 [Full text]
we should ask patients: Alejandro F. Luque-Coqui
bmj.com, 8 Jul 2003 [Full text]
Reducing cardiovascular disease by taking a "polypill" hope or hype?: Marcus Flather, et al.
bmj.com, 9 Jul 2003 [Full text]
The Polypill and prevention of Coronary Heart Disease: Daan Kromhout, et al.
bmj.com, 10 Jul 2003 [Full text]
Re: PolyPill may not decrease all-cause mortality: Alejandro F. Luque-Coqui
bmj.com, 10 Jul 2003 [Full text]
The fundamental principle of western medical science is the principle of scientific testing: Jeffrey Mann
bmj.com, 10 Jul 2003 [Full text]
Polypill for older adults.: Nandkishor V Athavale
bmj.com, 10 Jul 2003 [Full text]
Polypill versus conventional preventive care: Barry Lewis
bmj.com, 11 Jul 2003 [Full text]
Misplaced notions of simplicity, denial of complexity: Lawrence J. O'Brien, et al.
bmj.com, 11 Jul 2003 [Full text]
Incredulous of middle England !!: Saul G Myerson
bmj.com, 11 Jul 2003 [Full text]
Re: Re: Shame on you BMJ!!: Michael Bunbury
bmj.com, 12 Jul 2003 [Full text]
Questionable benefit from polypill treatment.: Uffe Ravnskov
bmj.com, 13 Jul 2003 [Full text]
The �polypill�: medical myth versus balanced judgement: Ian F Godsland, et al.
bmj.com, 14 Jul 2003 [Full text]
CARDIOVASCULAR PREVENTION AND THERAPY: Andrea Alberto Conti, et al.
bmj.com, 15 Jul 2003 [Full text]
Poly-drug to reduce cardiovascular disease: Dietmar Fuchs, et al.
bmj.com, 18 Jul 2003 [Full text]
The wonderful poly-pill: Miguel E. Campos, et al.
bmj.com, 19 Jul 2003 [Full text]
Potential Issues: Robert Kerr
bmj.com, 23 Jul 2003 [Full text]
Concept of Poly-Pill contrary to medical judgement: Munir E Nassar, M.D., et al.
bmj.com, 25 Jul 2003 [Full text]
The Nays Have It: John A. DePoy, BS, MSc, MBA, et al.
bmj.com, 26 Jul 2003 [Full text]
The �polypill� strategy in high-risk Australian CVD patients: Christopher M Reid, et al.
bmj.com, 28 Jul 2003 [Full text]
Markov models deserve scientific scrutiny too.: Christopher J Martin, et al.
bmj.com, 29 Jul 2003 [Full text]
Noncompliance with hypertensives: Christopher J Squire
bmj.com, 30 Jul 2003 [Full text]
Risks with the "Polypill" in the Oldest Old: Sven E Nilsson, et al.
bmj.com, 13 Aug 2003 [Full text]
delay vs prevention: gerry e burns
bmj.com, 15 Aug 2003 [Full text]
Why not Omega-3 fatty acid as part of Polypill ?: William K Smith M D
bmj.com, 17 Aug 2003 [Full text]
Enter...The 'Omnipill': Joseph .C. Obi
bmj.com, 18 Aug 2003 [Full text]
Omega-3 fatty acids and brown fat.: Richard G Fiddian-Green
bmj.com, 19 Aug 2003 [Full text]
We are headed toward a healthcare crisis fast enough, thank you.: Philip King, D.Ph.
bmj.com, 20 Aug 2003 [Full text]
A natural mini polypill: Potential impact on population cardiovascular risk of a daily drink of milk: Gary A Wright, et al.
bmj.com, 22 Aug 2003 [Full text]
The Polypill and Ayurdeva: Rajeev Gupta
bmj.com, 28 Aug 2003 [Full text]
What's really behind the antagonism for the polypill?: James G Penston
bmj.com, 1 Sep 2003 [Full text]
drug interactions: Teresa Tarnowski Goodell, RN
bmj.com, 18 Sep 2003 [Full text]
Reducing Cardiovascular Disease: William E. Feeman Jr., et al.
bmj.com, 19 Sep 2003 [Full text]
polypill - why not ? polypharmarcy is practised !: das sabapathy
bmj.com, 4 Oct 2003 [Full text]
Methodological issues remain unanswered: Tom Fahey, et al.
bmj.com, 31 Oct 2003 [Full text]
Polypill-Pr, a new formulation for the mature male: A. Mark Clarfield
bmj.com, 30 Jan 2004 [Full text]
Re: Polypill- adding osteporosis treatment restores gender equality at 8 all: Jeremy G Jones
bmj.com, 1 Feb 2004 [Full text]
Methodological issues remain unanswered - Authors' response: Nicholas J Wald, et al.
bmj.com, 8 Mar 2004 [Full text]
Polypill a life�in: Guy-Andr� Pelouze
bmj.com, 19 Mar 2004 [Full text]