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Rapid Responses: Rapid Responses published:
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Costing the polypill, £60 per year.
- john s ashcroft (27 June 2003)
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More Compelling Evidence
- William E. Osmun (27 June 2003)
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Beware the Epidemiology
- Bruce Bain (27 June 2003)
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Good news: All we need to do now is get people to prescribe it and then take it...
- Alexander M Clark (27 June 2003)
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correction to cost of prescribing polypill
- john s ashcroft (27 June 2003)
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Now who's playing God …
- Steve Taylor, Angela Konings (27 June 2003)
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Pilly Polly Doo Dah all the way
- Malcolm Kendrick (27 June 2003)
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PolyPill may not decrease all-cause mortality
- Eddie Vos (27 June 2003)
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Only 80% reduction? Why not go for 100%?
- Barry A Groves (27 June 2003)
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Whose Life Is It Anyway? The Polypill May Increase Health Inequalities
- Michael A Soljak (27 June 2003)
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Shabby Medical Thinking
- Nicholas M Regush (27 June 2003)
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A gauntlet thrown at drug companies or doctors?
- Richard G Fiddian-Green (28 June 2003)
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The 'Vacca Foeda' PolyPill
- Joseph .C. Obi (28 June 2003)
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Impact of single normal dose blood pressure medications
- Bala Subramanian (28 June 2003)
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Polypill drawbacks and multivitamin as alternative
- BIll Sardi (28 June 2003)
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The Big Issue
- Dan Rutherford (28 June 2003)
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new paradigm
- Martin R Innes (28 June 2003)
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Dumbfounded
- Peter J Hosein (28 June 2003)
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Can anyone afford to live a very long life?
- Mark Hochhauser, Ph.D. (29 June 2003)
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A Sad Day For British Medicine
- Allan Withnell (29 June 2003)
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Also dumbfounded
- Margaret J Tyson (29 June 2003)
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Treat people not populations
- Eugene A. Rybinski (29 June 2003)
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polypill ; for all races, sexes and seasons ?
- Adesuyi Ajayi, Southern Univ. 3100 Cleburne Ave, Houston TX77004 (29 June 2003)
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Old joke and current practice
- Adrian K Midgley (29 June 2003)
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What do we die then?
- Roger Wanner (29 June 2003)
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WHEN?
- Linda L Gimnich (30 June 2003)
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About as believable as the tooth fairy
- Adam Jacobs (30 June 2003)
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A pill a day keeps health away?
- Ewan Hamnett (30 June 2003)
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Shame on you BMJ!!
- Michael C Bunbury, Me (30 June 2003)
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Nearer 66% rather than 88% IHD risk reduction after 2 years?
- Eric S. Kilpatrick (30 June 2003)
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POLYPILL, AN IDEA, PERHAPS A VERY GOOD ONE, BUT NOT A JOKE
- CELIO LEVYMAN,MD,MSc, CEP 06454-030 (30 June 2003)
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Relative risks and meta-analysis
- J Michael Henk (30 June 2003)
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Unbelievable and unachievable
- Mark J Garton (30 June 2003)
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Multiple Polypill Benefits
- Gerard T O'Brien (1 July 2003)
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WHO should convene an aspirin meeting?
- Gareth P Morgan (1 July 2003)
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POLYPILL AGAIN,BUT IN THE THIRD WORLD
- CELIO LEVYMAN,MD,MSc (2 July 2003)
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Patients before populations
- Peter N Trewby, Catherine Trewby (2 July 2003)
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Polypill treatment and the physical properties of blood.
- Leslie.O. Simpson (2 July 2003)
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Re: Shame on you BMJ!!
- Daniel Weyandt (2 July 2003)
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Reality check
- Mike Schachter (2 July 2003)
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Brave New World
- Joachim P Sturmberg (2 July 2003)
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Polypill Choices
- Shah M Tauzeeh (2 July 2003)
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Concept is correct
- Paul W Masters (2 July 2003)
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Logical consequence of current polypharmacy
- Dr. Matthew L Grove (2 July 2003)
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What must be done now.
- William Plummer (2 July 2003)
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Aspastatapril vs Polypill
- Ketan K Dhatariya (2 July 2003)
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Compliance with the Polypill
- Anita Sainsbury (3 July 2003)
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Re: What must be done now - correction.
- William Plummer (3 July 2003)
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Is The Paper a Spoof?
- David A Brodie (3 July 2003)
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Dubious mathematical assumptions
- David M Reith (3 July 2003)
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Total Mortality
- Jeffrey R Johnstone (4 July 2003)
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Modelling and assumptions need clarification
- Tom Fahey, Alan Montgomery, Yoav Ben Shlomo (5 July 2003)
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Polypill Debate
- Stephen J Redmond (5 July 2003)
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Cat amonsgt the pigeons
- Adam L Brown (5 July 2003)
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Eradicating cardiovascular disease with polypharmarcy: Dream or reality ?
- Peter Marckmann (6 July 2003)
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Willing suspense of disbelief
- Elved B Roberts (7 July 2003)
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'Magic pill' approach would shift focus from proven and cost-effective CVD prevention
- Derek Yach, Shanthi Mendis, JoAnne Epping, Ruth Bonita, Amalia Waxman (7 July 2003)
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Salicylate deficiency
- Gareth P Morgan (7 July 2003)
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we should ask patients
- Alejandro F. Luque-Coqui (8 July 2003)
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Reducing cardiovascular disease by taking a "polypill" hope or hype?
- Marcus Flather, Anil. K. Taneja, Diego Perez de Arenaza (9 July 2003)
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The Polypill and prevention of Coronary Heart Disease
- Daan Kromhout, Henry Blackburn, Alessandro Menotti, and Hugo Kesteloot (10 July 2003)
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Re: PolyPill may not decrease all-cause mortality
- Alejandro F. Luque-Coqui (10 July 2003)
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The fundamental principle of western medical science is the principle of scientific testing
- Jeffrey Mann (10 July 2003)
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Polypill for older adults.
- Nandkishor V Athavale (10 July 2003)
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Polypill versus conventional preventive care
- Barry Lewis (11 July 2003)
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Incredulous of middle England !!
- Saul G Myerson (11 July 2003)
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Misplaced notions of simplicity, denial of complexity
- Lawrence J. O'Brien, Arlington, VA 22209 (11 July 2003)
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Re: Re: Shame on you BMJ!!
- Michael Bunbury (12 July 2003)
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Questionable benefit from polypill treatment.
- Uffe Ravnskov (13 July 2003)
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The ‘polypill’: medical myth versus balanced judgement
- Ian F Godsland, Victor Wynn (14 July 2003)
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CARDIOVASCULAR PREVENTION AND THERAPY
- Andrea Alberto Conti, Gian Franco Gensini (15 July 2003)
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Poly-drug to reduce cardiovascular disease
- Dietmar Fuchs, Schroecksnadel Katharina, Frick Barbara (18 July 2003)
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The wonderful poly-pill
- Miguel E. Campos, None (19 July 2003)
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Potential Issues
- Robert Kerr (23 July 2003)
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Concept of Poly-Pill contrary to medical judgement
- Munir E Nassar, M.D., N/A (25 July 2003)
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The Nays Have It
- John A. DePoy, BS, MSc, MBA, Milwaukee, WI 53217 (26 July 2003)
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The “polypill” strategy in high-risk Australian CVD patients
- Christopher M Reid, Sloane Birrell, Melinda D. Rockell (28 July 2003)
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Markov models deserve scientific scrutiny too.
- Christopher J Martin, French J, Vanderpump M (29 July 2003)
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Noncompliance with hypertensives
- Christopher J Squire (30 July 2003)
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Risks with the "Polypill" in the Oldest Old
- Sven E Nilsson, Stig Berg (13 August 2003)
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delay vs prevention
- gerry e burns (15 August 2003)
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Why not Omega-3 fatty acid as part of Polypill ?
- William K Smith M D (17 August 2003)
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Enter...The 'Omnipill'
- Joseph .C. Obi (18 August 2003)
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Omega-3 fatty acids and brown fat.
- Richard G Fiddian-Green (19 August 2003)
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We are headed toward a healthcare crisis fast enough, thank you.
- Philip King, D.Ph. (20 August 2003)
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A natural mini polypill: Potential impact on population cardiovascular risk of a daily drink of milk
- Gary A Wright, Allan D. Struthers (22 August 2003)
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The Polypill and Ayurdeva
- Rajeev Gupta (28 August 2003)
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What's really behind the antagonism for the polypill?
- James G Penston (1 September 2003)
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drug interactions
- Teresa Tarnowski Goodell, RN (18 September 2003)
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Reducing Cardiovascular Disease
- William E. Feeman Jr., William E. Feeman, Jr., M.D. (19 September 2003)
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polypill - why not ? polypharmarcy is practised !
- das sabapathy (4 October 2003)
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Methodological issues remain unanswered
- Tom Fahey, Alan A Montgomery, Yoav Ben-Shlomo (31 October 2003)
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Polypill-Pr, a new formulation for the mature male
- A. Mark Clarfield (30 January 2004)
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Re: Polypill- adding osteporosis treatment restores gender equality at 8 all
- Jeremy G Jones (1 February 2004)
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Methodological issues remain unanswered - Authors' response
- Nicholas J Wald, Malcolm R Law, Joan K Morris (8 March 2004)
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Polypill a life…in
- Guy-André Pelouze (19 March 2004)
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john s ashcroft, general practitioner old station surgery,heanor rd, ilkeston,derbyshire,DE7 8ES
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Wald and colleagues make no attempt at pricing the polypill, or the costs of treating all people in the UK over the age of 55, as they propose. As they point out many of the agents you may wish to use are of patent. With the help of the BNF, and a few helpful internet sites (www.21.cep.com/drug) I have attempted to do this. The BNF price of a bendrofluazide 2.5mg tablet is 2.5p and includes the cost of packaging, calender pack and patient information leaflet. Adding in extra components at there bulk ingredient cost per tablet the beta blocker, bisoprolol, 5mg @ $2,800/kg....0.67p the ACE inhibitor, lisinopril,5mg @ $2,200/kg....0.5p aspirin 75mg adds a suprising 0.5p/tablet, while folic acid 0.8mg, only 0.1p. Simvastatin adds to the bulk of the cost, but as from may 2003 it is off patent and available as generic.In bulk 40mg of simvastatin at $2450/500g adds 12p/tablet, for a grand total for this polypill of 16.4p/day or £60/year. Approximately one third of the UK population is over the age of 55 years,or 20 million people. The polypill as discribed here would cost the NHS approximately £120 million/year. Considering the NHS spent £571 million on lipid lowering drugs alone last year, this should not be a problem, indeed the NHS would save £450 million/year if the polypill was available. However, a note of caution, the price of ingredients has little to do with price the NHS decides to pay, even for of patent drugs, The NHS is still paying £29.69 for 28days of simvastatin at only 20mg, while even the US Millitary pay only pay approximately £7.50 on their contract with Merck & co.(www.pec.ha.osd.mil), and over £25/pack of omeprazole 20mg, even though it has been of patent for more than a year, and parmacists are paying less than a quarter of that price. Competing interests: None declared |
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William E. Osmun, Assistant Professor, University of Western Ontario Mount Brydges, ON N0L 1W0
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I am just wondering if the 'compelling' observational evidence that lowering serum homocysteine reduces heart disease is as 'compelling' as the observational evidence that estrogen did the same thing. Competing interests: None declared |
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Bruce Bain, Senior Medical Officer 8 Wing Medical Squadron, 8 Wing Trenton, Trenton,ON, Canada
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Sir, I read with interest the article by Wald and Law. A fascinating analysis. However, I can't help but think of the statistical data presented to us a few years ago concerning the DEFINITE benefit regarding cardiovascular disease that we could achieve if we put all our post-menopausal female patients on hormone therapy! I believe it is very dangerous to take bits and pieces of research and cobble it together and come up with a major conclusion such as this. Although I agree there are premature deaths due to cardiovascular disease, surely something has to get us in the end! There will always be a "Number One" cause of death; we are not, after all, immortal. I suspect if we could get everyone a bit more active and outlaw smoking, we would see some very dramatic changes. Indeed, cardiovascular disease already seems to be on the wane (according to some other epidemiologists!). However, the authors are probably correct in saying the population at large would probably rather just take a pill, as we do for so many other things these days. I'm sure the drug companies will be ecstatic having all of us taking medication once we hit 55. Shares in Glaxo-Wellcome anyone? Competing interests: None declared |
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Alexander M Clark, Assistant Professor Facult of Nursing, University of Alberta, Edmonton, AB. Canada. T6G 2G3
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The paper by Wald and Law 1 details a creative yet sensible approach to reduce cardiovascular disease. The evidence for the cost-effectiveness of the drugs that are proposed to be included in the Polypill is well established and the idea for general provision to those over 55 years of age well placed. However, to what degree a single pill constitutes a strategy is debatable. Medications for cardiovascular disease that have been known to be effective for some years are often not prescribed 2 nor taken by patients 3. These patterns are identified across all fields 4. Though provision of medication via a single pill is likely to increased compliance, patient beliefs regarding medications exert a very strong influence on whether medications are consumed 4. Further, medications are least likely to be taken if they are preventative as opposed to curative4. Any strategy that aims to reduce cardiovascular disease by 80% therefore requires to address not only medications but health care systems, professionals and patients. Using a approach based on concordance 5 6, professionals need to acknowledge the influence of patients’ beliefs and attempt to come to mutual agreements about medication regimen. 1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. British Medical Journal 2003;326:1419. 2. Euroaspire II Study Group. Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries. European Heart Journal 2001;22:554-572. 3. World Health Organisation. Adherence to long-term therapies: evidence for action. Geneva: WHO, 2003. 4. Cater S, Taylor D, Levenson R. A question of choice- compliance in medication taking. London: Medicines Partnership, 2003. 5. Mullen PD. Compliance becomes concordance. BMJ 1997;314:691. 6. Royal Pharmaceutical Society of Great Britain. From compliance to concordance : towards shared goals in medicine taking. London: RPS, 1997. Competing interests: None declared |
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john s ashcroft, general practitioner old station surgery,ilkeston,derbyshire,DE723EA
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The cost of prescribing to 20million people a polypill costing £60/year is £1200 million/year. Competing interests: None declared |
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Steve Taylor, GP Auckland, New Zealand, Angela Konings
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The implications of Wald & Law's paper are truly monumental. Whilst scientifically brilliant and Nobel-ian in their relevance, they are simultaneously unsettling and even alarming. The impact of such a low-cost initiative upon individual and population based health parameters is potentially enormous. But having, at a stroke, (to coin a phrase), slashed the risk of cardiovascular disease – what then for humanity? Will everyone be that much healthier, happier and productive in their lives? As GPs we have many patients nowadays whose cardiovascular problems have been managed by control of their blood pressure, reduction of their LDL and the use of aspirin. Yet they continue to get older, and they continue to develop other problems - often of a serious, debilitating, and very long term nature. We can be sure that the pharmaceutical companies, having 'lost' the cardiovascular market to the low-cost generic polypill, will concentrate their efforts on other avenues, so is it only a matter of time before we hear of suggestions to produce 'polypill mark 2'? Perhaps containing glucosamine and chondroiton, a cox-2 inhibitor, a proton pump inhibitor, a calcium homeostatic agent, a memory enhancing agent and others? And, for this part of the world, something to prevent the total failure of the skin induced by UV exposure? And how long will it before the polypill becomes a part of veterinary science? We're all still mortal and perhaps as clinicians this is the most important message for us all to remember. Which is more important: quality or quantity of life? Or how do we achieve a balance in that? Because it's not science that poses the hardest questions, it's the ethics and morality of what we are doing. Doctors used to be accused of 'playing God', although for a generation or more society has done its reasonable best to knock that out of us. But, perhaps its time has come again? Competing interests: None declared |
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Malcolm Kendrick, Medical Director Adelphi Lifelong Learning Adelphi Mill, Bollington, Macclesfield, Cheshire SK10 2TH
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It is almost impossible to know where to start in responding to this article. I will restrict myself to one part of their polypill concept, namely the benefits of blood pressure reduction. I will quote, highlights, from the European Heart Journal. 'Stamler stated 'the relation of SBP to risk of death is continuous, graded and strong, and there is no evidence of a threshold... The formulation of this 'lower the better' principle, in terms of the linear logistic model is the paradigm for the relationship of all cardiovascular risks to blood pressure and forms the foundation for the current guidelines for hypertension... Twenty years ago Keys, using simple graphical methods, concluded that the linear model, in terms of the relationship of overall and coronary heart disease death to blood pressure was unjustified. Could Keys be correct? To see, we reexamined data from the Framingham Heart Study. That carefully conducted and most widely cited study played a seminal role in firmly entrenching the current linear thinking on blood pressure.... We limited our analysis to the 18 year follow-up data. The use of the full (34 year) data would have introduced serious confounding in the natural relationship of cardiovascular risk to blood pressure, which was our primary interest. Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact, these data actually statistically rejected the linear model. This fact has major consequences. Statistical theory now tells us that the paradigm MUST be false for the target population of the study.' Port S et al 'There is a non-linear relationship between mortality and blood pressure' European Heart Journal (2000) 21 1635 - 1638 In the area of blood pressure reduction Law and Wald are using a model of blood pressure reduction that is almost certainly wrong. I believe that their other models are also wrong, but this is a rapid response, not a PhD thesis. Yet, on the basis of a horribly flawed analysis Law and Wald recommend that everyone in the Western World should be taking six different drugs for the rest of their lives. Any moment now I am expecting an article to appear in the BMJ written by the Red Queen, entitled 'Everyone is ill, and all shall have medication.' Competing interests: None declared |
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Eddie Vos, maintains http://www.health-heart.org Sutton (Qc) Canada J0E 2K0
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While folic acid [with vitamins B2, B6 and B12] lowers homocysteine which well may be causal to athero-sclerosis, non of the other ingredients of PolyPill [aspirin, statin, blood pressure drugs] deal with underlying root causes of vascular disease. Even in "high risk" populations, statins failed to reduce OVERALL mortality in ALLHAT, PROSPER and ASCOT while numbers needed to treat for 1 year to postpone one death in HPS was about 300. These are the last 12 months of statin trials. The concept of all-cause mortality is glaringly missing in the Law/Wald analysis. Maybe, Editor Smith's editorial idea is a good one: adding red wine in a pub would raise HDL-cholesterol. Let me propose that jogging from pub to pub would add another HDL raising exercise component while avoiding the danger of driving on heart-healthy alcohol, but not that of liver toxicity and addiction for some. In any approach, from statin via alcohol to aspirin, the focus should be on overall health, overall mortality and safety, and only the multivitamin/folic acid approach is totally safe while dealing with underlying processes, in part or largely through proven homocysteine reduction. Competing interests: None declared |
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Barry A Groves, Independent researcher OX7 6LP
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I have read some rubbish in my time, but this just about takes the biscuit. Let’s take this to its logical conclusion and put every drug known to medical science in the water supply. That way we will prevent and cure every disease Man is subject to. And we can all live happily ever after. Diseases will be abolished overnight; doctors will all be redundant; the NHS will no longer need vast sums of money, and we will all be, not only healthier, but wealthier. Or, of course, we could cut mortality by 100% by preventing the most important “risk factor” of them all – being born. Competing interests: None declared |
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Michael A Soljak, Consultant in Public Health Medicine North West London Strategic Health Authority
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Assuming that the strategy advocated by Wald and Law in their paper in this week's BMJ (1) is cost-effective, a major concern is that its implementation may further increase socieoeconomic inequalities in health. Two small surveys have investigated the absolute benefits of treatment different groups would require before starting treatment themselves. A survey in Norwich showed that the threshold for numbers needed to treat chosen by consultant physicians was twice that chosen by general practitioners and three times that chosen by nurses and the public (2). In a survey in London general practices, doctors and other health professionals chose treatment for smaller absolute benefits than patient groups; patients from an inner city practice chose higher benefits than patients from a suburban practice, and homeless people chose the highest absolute benefits (3). It is likely that these differences are a result of confounding with socioeconomic class. A recent review of patient involvement in decision- making noted that research in this area has underemphasised the effects of social structure in the construction of health beliefs and subsequent behaviour, as well as the effects of sociodemographic characteristics, social circumstances, and group influences (4). In their review of the relation between income and health, Marmot and Wilkinson show that a consistent finding of analyses of how subjective well-being varies with income is that richer people are, on average, more satisfied with their lives than their poorer contemporaries (5). It seems plausible that patients "quality adjust" the predicted benefits of preventative healthcare on the basis of their personal expectations of the life years to be gained. Wald's and Law's proposal therefore has major political and ethical implications which should be widely debated. In the absence of a radical improvement in the expectations of the relatively poor, is saving a wealthy life year more valuable? Or should NHS resources be directed at reducing inequity in life expectancy by persuasion if necessary? 1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003;326:1419-0. 2. Steel S. Thresholds for taking antihypertensive drugs in different professional and lay groups: questionnaire survey. BMJ 2000;320:1446-1447. 3. Lewis DK, Barton S. Who decides when to start preventive treatment? A questionnaire survey to compare the views of different population subgroups. J Epidemiol Comm Health 2003;57:241-242. 4. Bowling A, Ebrahim S. Measuring patients' preferences for treatment and perceptions of risk. Quality in Health Care 2001;10:i2-i8. 5. Marmot M, Wilkinson RG. Psychosocial and material pathways in the relation between income and health: a response to Lynch et al. BMJ 2001;322:1233-1236. Competing interests: None declared |
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Nicholas M Regush, Editor, redflagsdaily.com Montreal, Canada H3G 1Z9
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What is this wonder pill all about? It's a combination pill that everyone over the age of 55 (or younger) would take – and could reduce the incidence of cardiovascular disease by over 80%. Really? Is there actual direct data for this humdinger? No, there is not. The authors propose this idea based on a review of other studies, and strangely believe that the indirect data all could add up to a huge reduction in the incidence of cardiovascular disease. This has got to be one the most egregious presentations that I have ever come across in all my years as a health reporter, both in the print world and at ABC News in New York. That the authors actually appear to have the support of the editor of the British Medical Journal is truly amazing – and dangerous. All these so-called health professionals actually have convinced themselves that if you put six different drugs together, they will all add up to one big cure of sorts. This is not only junk science at its worst, but reveals the sloppy intellectual processes going on these days in medical science, in focusing attention on such complex issues (and controversial ones, I might add) surrounding cardiovascular disease. Furthermore, to assume that each and every one of these drugs used for different strategic purposes in the battle against heart disease is, for one thing, the best approach in providing treatment for heart trouble, and then to assume that you can batch them, on the basis of what they appear to be doing on their own, is Fool’s Gold. Can we please have some real science conducted, preferably research that deals with safety and efficacy before we become enchanted with a polypill idea? Any serious discussion about incorporating a variety of theories about cardiovascular disease into one product package, which is what this entire issue amounts to, reveals a total disregard for scientific principles and for the human condition, which is far more complex than these authors seem to think. Competing interests: None declared |
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Richard G Fiddian-Green, None None
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The Polypill is an appealing idea but specifically addresses risk factors for cardiovascular diseases to the exlusion of other diseases notably cancers. Furthermore whilst not specific for statins per se there was a trend (p=0.06)towards an increase in suicides, accidents, and trauma in a meta-analysis of the effects of cholesterol reduction on mortality from all causes(1). There are rational reasons, inhibition of coenzyme Q synthesis, for believing that there may well be an increased risk in suicides, accidents, and trauma and other causes of mortality associated with statin usage (2,3). The longer the usage the greater the risks, and it is early days yet in the statin trials. There may also be a risk of developing chronic diseases such as heart failure, that is echocardiographic evidence of altered myocardial size and function. The authors acknowledge that they are treating risk factors, which might be effects which may well be secondary causes, rather than the primary cause of the cediovascular diseases. Anytime one treats an effect rather than a cause there is a risk of unintended consequences, such as an increase in suicides, accidents and trauma. Until the primary cause or causes of all diseases is defined, and that could be closer to reality than commonly supposed, the sooner doctors will stop flying by the seat of our pants as they have done since antiquity. I would not bet on this issue being the most important issue of the BMJ in decades unless the Polypill has been proposed with the specific intent of provoking a legal confrontation with the drug industry. It is not the drug companies that are at fault. It is us, the doctors. 1. Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials Matthew F Muldoon, Stephen B Manuck, Aaron B Mendelsohn, Jay R Kaplan, and Steven H Belle BMJ 2001; 322: 11-15. 2. UPDATE: Statins Lack Mortality Benefit Eddie Vos bmj.com/cgi/eletters/321/7267/983#29001, 22 Jan 2003 3. Re: update on statins and mortality Richard G Fiddian-Green bmj.com/cgi/eletters/321/7267/983#29013, 22 Jan 2003 Competing interests: None declared |
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Joseph .C. Obi, Chief Consultant WellnessClinics.co.uk
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10.1mg of Common Sense 22.5mg of Epidemiology 15.6mg of Critical Appraisal 49.5mg of Biostatistics 77.2mg of Pharmacology 94.8mg of Remorse Dosage: One wee little capsule daily. Swallowed whole. Duration : For Life Indication: 'Tiresome' and 'Under-employed' Editors Competing interests: Dr Joseph Chikelue Obi MBBS MD MPH DSc FRIPH is also the Chairman of the General Wellness Assembly (GWA); an International Professional Body for Independent Wellness Consultants |
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Bala Subramanian, Consultant cardiologist(Retired) Harrow HA3 9XE
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I have been advocating and using a combination of statins, folic acid, aspirin and a blood pressure lowering drug such as beta blockers, calcium channel blockers or ace inhibitors if indicated for over 8 years. I normally use full dose antihypertensive medication usually in combination therapy in hypertensives, ACE inhibitors in heart failure and beta blockers to control synptoms of Ischaemia.
Such strategies in non surgical management of Ischaemic heart disease over the last 10 years have yielded extremely favourable results in my patients and I have advised a company to market a polypill with 4 components named 4URHEART which is commercially available.
A question to the authors:How is the risk modified by use of either one or two drug antihypertensive treatment in hypertensives and what is the risk factor reduction if any in normotensives?
What are the side effects in persons with low blood pressure?
The authors have come to a conclusion that use of three antihypertensive medications in lower than normal therapeutc doses has the same effect as full dose of a single drug. This is an important statement and would encourage the widespread use of these drugs as indicated in the article.
I congratulate the authors for an extremely important and practical contribution.
Bala Subramanian
Competing interests: None declared |
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BIll Sardi, President, Knowledge of Health, Inc. 457 W. Allen Ave. #117 San Dimas, CA 91773 USA
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The originators of the polypill (5 drugs + 1 vitamin) concept have launched a rather admirable and bold attempt to prevent rather than just detect and treat cardiovascular disease. Yet, according to the Drug- Induced Nutrient Depletion Handbook, 2nd edition (2001, Lexi-Comp), some of the ingredients in the polypill could induce shortages of nutrients essential for cardiovascular health. Examples are statin drugs which deplete coenzyme Q10, diuretics which deplete electrolytes (magnesium and potassium), aspirin which depletes folic acid, potassium and vitamin C. The projected 80 percent reduction figure in cardiovascular risk needs to be clarified since the studies cited to substantiate the polypill used relative reduced risk data rather than hard numbers. Out of 100 users of polypill, how many could be expected to benefit (alleged 11-years of added life)? -- Bill Sardi Competing interests: No direct competing financial interests (write and sell books on nutrition) |
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Dan Rutherford, GP & MD of www.netdoctor.co.uk St Andrews, Fife, KY16 8LP
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No government, or doctor, has to my knowledge ever received a mandate from the public to restrict medical care based on the principle of treating the most 'at risk' first (this is never more than a smoke screen for inadequate resources). It's therefore to the good that Wald & Law propose a risk reduction treatment across the board, subject only to clinically sensible restrictions on who should get it. One thing worries me though. Why have they patented this idea? I'll be suitably impressed if it's to prevent Big Pharma from doing the same thing and profiting from something that potentially should be cheap and very widely affordable. Of course that'll also mean that they hand over the patent to the World Heath Organisation or the like who can administer it for the public good. Competing interests: None declared |
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Martin R Innes, GP-Principal Ravenswood Surgery Johnstone PA5 8SO
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I was under the impression that "new paradigm" thinking involved "mind/body/spirit" approaches . Indeed the BMJ of Christmas 2002 stated if we did not address spiritual issues concerning our patients , we were missing the boat.The Japanese are classified as the healthiest nation-can we find anything in their philosophy that entertains polypills-I think not.Are we not to learn from those that are successful? And what happened to the notion of encouraging the body's own natural healing responses? It is one of the tenets of complementary medicine-and the public do seem to be responsible for a significant rise in it's popularity(they seem to know what the like).Or are we to stick with the same old Cartesian model .I ,for one , will stick with trying to assist the body in helping itself . Competing interests: None declared |
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Peter J Hosein, SHO Trinidad, West Indies.
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I would like to add my voice to those who are truly dumbfounded that an article like this could find its way into the pages of the BMJ, with the whole hearted support of the Editor. I first learnt of the Polypill while watching CNN over breakfast this week and I scurried over to the BMJ's website, expecting to find a well designed prospective trial evaluating this wonder pill...only find a series of meta-meta-analyses and promises of theoretical benefit for a combination drug that has not yet been formulated. If this is the most important BMJ issue for 50 years then I'm glad that I never had a subscription. I will save my enthusiasm for the day when the evidence for efficacy and safety of the Polypill is published. Competing interests: None declared |
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Mark Hochhauser, Ph.D., Readability Consltant Golden Valley, MN USA 55422
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The Polypill, if successful, may add decades to a patient's life. While this may be a desirable end medically, a relatively rapid extension of everyone's lifespan has monumental societal consequences. If this pill extended the average lifespan to 100, people would spend about 35 years in retirement--but can people save enough money during 45 years of work to pay for 35 years of retirement? The US Congress is debating ways to pay for prescription drugs for Medicare patients, many of whom are spending a large percentage of their income on prescriptions. Will patients be able to pay prescription drugs costs for the one-third of their life they'll be retired? If people live to be 100, it won't be unusual to have two (or even three) retired generations in the same family. Will employees be able to pay the huge payroll taxes needed for Social Security and Medicare benefits for their retired parents and grandparents? Will employers be able to offer employee health benefits after retirement if such benefits continue for 35 years? An effective Polypill will have consequences for families, communities, health care systems, social service agencies, businesses and goverment programs, impacting virtually every part of society in ways that have not yet been identified or addressed. Competing interests: None declared |
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Allan Withnell, Retired Compton Court, Compton Green, Gloucester. GL19 3JB
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EDITOR-Your editorial marks a sad day for British Medicine(1 We shall never reduce the increasing costs of the NHS unless we encourage people to take more responsibility for their own health. Nathan Pritikin and others have shown that it is possible to prevent and cure coronary heart disease and other degenerative diseases by diet and exercise alone. The reasons with references are set out in my recent paper(2). (1)Editoral. BMJ 28 June 2003. (2)Withnell,A.(2003). The Natural Cure of Coronary Heart Disease. Nutrition and Health, Vol.17, pp.55-60. Competing interests: None declared |
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Margaret J Tyson, Director The Orchard, Woodseats Lane, Charlesworth, Glossop SK13 5DP
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I would like to say that I couldn’t agree with “Dumbfounded” more! Without a full trial how can the claim be made that cardiovascular risk is reduced by 80% by the “Polypill”. Haven’t the authors heard of synergistic and antagonistic effects? Secondly, if the Polypill were brought into existence people would feel free to eat what they felt like, lower exercise levels and forget all previous advice. This would lead to an increase in obesity and more particularly of Diabetes II with all its effects. We would therefore see an increase in limb loss, blindness, kidney problems etc. This could lead to a cancelling out of any benefits of the Polypill. The Polypill is a recipe to increase patients’ dependence on the NHS when a preventive lifestyle should be hammered home so that people take responsibility for their own lives. And where this is unsuccessful what’s wrong with diagnosing and prescribing medications for individual lifestyle problems? Isn’t the NHS supposed to be about treating the individual? Competing interests: None declared |
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Eugene A. Rybinski, General Practitioner Burncross Surgery,Sheffield,S35 1RN
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Wald and Law's 'polypill' is an intriguing proposition.Their calculations are based on pooled data in large populations. While it may be true that age is the single most predictive factor for the development of cardiovascular disease,within group variation is likely to be large.Where it may not be possible to separate populations on the basis of multivariant analysis, individuals with low and higher abolute risk can be identified. As epidemiologists Wald and Law do not have to concern themselves with the difficult matter of dealing with individual patients,some of whom are well informed and may pose searching questions.I suspect that most subjects would not be interested in taking a 'polypill' in order to reduce the population burden of disease.People are more likely to be concerned with their own individual absolute risk of disease,the treatments which may safely reduce that risk and the burden of costs they have to incur in order to obtain the benefit. If all those over 55years are treated then a large number with low absolute risk will incur no benefit.I propose that the well informed customer would prefer to go for individual risk analysis,a policy that may thwart well intentioned epidemiologists. Competing interests: None declared |
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Adesuyi Ajayi, Adjunct Professor of Medicine/ Sr Scientist Ctr for CardiovascularDiseases, Texas, Southern Univ. 3100 Cleburne Ave, Houston TX77004
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Drs Wald and Law are to commended for the rare insight and ingenuity, in the advocacy of polypill to prevent and treat cardiovascular diseases. There are however, unanswered questions regarding the global applicability of their proposed pill , by ethnicity and gender. There are established racial differences in the monotherapeutic response to ACE inhibitors and beta -blockersin hypertension. Blacks respond poorly and the Chinese respond perhaps too well. Whites are intermediate. Aspirin efficacy may be gender dependent, since TXA2 receptors is under androgenic regulation and also exhibits a pharmacogenetic polymorphic response. Aspirin may also negate the beneficial actions of ACE inhibitors. Moreover, the benefit estimated at 80% reduction in cardiovascular end points may be an overestimation, because drugs such as aspirin and statins and ACE inhibitors may diminish platelet aggregation and thrombosis through Nitric oxide production as the final common path. Redundancy, may thus cause a less than additive beneficial cumulative effect. In blacks other risk factors are not factored in , such as the sickle cell trait [ hemoglobin genotype AS ] which acts as a subliminal accelerator of vascular disease and organ damage. I therefore strongly opine, that large multi-centered clinical trials in all races, gender should be conducted before the quantification of the benefits of this fixed drug combination can be known. It may be that many variants [ containing different doses of same constituents ]of the polypill may be the final answer to cardiovascular disease scourge in the 21st century. Prof AA Leslie Ajayi MD, Ph.D. Competing interests: None declared |
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Adrian K Midgley, GP Exeter EX1 2QS
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There has always been an element of truth in the old and slightly cynical description of "Gerifix" and "Gerifix Forte" - the common collection of medicines that many elderly medical patients find themselves on in and after hospital. Outside hospitals, in the effort to achive reductions in premature or avoidable cardiovascular death and disability we find there are many people who are actually taking all or most of the components of the "Polypill", and we have reasonable grounds to believe deriving benefit at least in the mass from doing so. Incredulous SHOs may yet hear of all these things, and may also learn that meta-analysis is commonly more reliable than inspecting the results of a single trial, particularly if its power is low. Good paper. There are a lot more bits of wisdom camouflaged as cynicism in the profession, and subjecting these "folk-stories" to scientific analysis is at least entertaining. Competing interests: None declared |
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Roger Wanner, student Switzerland
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Before the time of polypill cardiovascular events killed 50 percent of britains citizens. So what will be the causes of death in the next century? Diing of Polypills intoxication? Competing interests: None declared |
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Linda L Gimnich, Principal, TMNG 75243
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Please advise WHEN this would be available in the US OR could be purchased elsewhere. Being OVER 55, we do not want to waste any time, and take any more chances than necessary. Already have a high blood pressure problem & cholesterol, we REALLY want and need this....along with the rest of the population! THE WORLD REALLY NEEDS THIS.........NOW! Competing interests: None declared |
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Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ
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It almost seems unnecessary to read any further than the title of Wald and Law’s paper to realise that it must be deeply flawed. The maxim ‘If it seems too good to be true, then it probably is’ tells us that anything claiming to reduce cardiovascular disease by more than 80% is unlikely to stand up to scrutiny. First, we are expected to believe that the relative risks of the separate ingredients are multiplicative. What is the evidence for this? It seems to rely on a failure to find modification of the effect of reducing one risk factor by the level of other risk factors. However, detecting such a difference (a statistical interaction term) usually requires greater statistical power than detecting a main effect. Were the trials Wald and Law cite in support of their claim adequately powered to detect the interactions? I doubt it. Looking closely at their suggestion that a statin can reduce IHD events by 61% shows more flaws. This seems to be based on the reduction expected on the basis of cohort studies if the reduction in LDL cholesterol of 1.8 mmol/l were achieved. First, the figure of 1.8 mmol/l is based on reductions achieved in patients with high LDL cholesterol, but we are told the Polypill is suitable for everyone irrespective of their cholesterol. And why look at cohort studies, with all their inherent biases and confounding, when we could look at randomised trials? In their subsequent paper, Wald and Law present the much less impressive data from randomised trials, which shows reductions in IHD events of about 20–30%. Only in a subset of trials selected on the basis of showing a large treatment effect did the reduction in IHD risk reach 50%. And does the claim of a 46% reduction in IHD from the antihypertensive components of the pill stand up to scrutiny? Well, no. It assumes that the antihypertensive effects of the three drugs are additive. In their third paper, Wald and Law present data showing that combinations of two drugs are additive (although not convincingly so), and then go on to make the untested assumption that combinations of three drugs would also be additive. And again, the expected reduction in blood pressure is based on patients with high blood pressure at baseline, and reductions in event rates are based on cohort studies, not on randomised trials. All this makes me wonder whether this paper was ever meant to be taken seriously. Perhaps it was simply part of an elaborate experiment designed to discover what the reaction of the journal’s readership and the popular media would be if a respectable medical journal published a load of complete bollocks. Competing interests: None declared |
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Ewan Hamnett, GP Principal Lordswood Medical Practice,54 Lordswood Road ,Birmingham ,B17 9DB
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If we were guaranteed never to have an accident or get caught for speeding would we drive slower? If I could print unlimited money in my attic would I spend less? If a pill is produced to reduce heart attacks by 80% will we excercise more and eat less? Richard Smith says this is a memorable BMJ.He may be right.This may be the day that the medical profession joins forces with the car and video game manufacturers to create a truly sedentary society! Competing interests: None declared |
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Michael C Bunbury, GP St Vincent, Me
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I am truly surprised that evidenced based medicine has taken such a strong grip on medical intelligence that even the editor of the BMJ could sanction a conclusion that defies even common sense. Conclusion: 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. So the message is "carry on smoking , grow fat on carbohydrates and hydrogenated fats and take a pill and you will live a normal healthy life?" Competing interests: None declared |
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Eric S. Kilpatrick, Consultant in Chemical Pathology Department of Clinical Biochemistry, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK
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The main study finding of the paper by Wald et al(1) is shown in their table 1, where it is stated that 88% of IHD events and 80% of strokes can be avoided after 2 years of ‘Polypill’ treatment at age 55-64. I cannot help but question the validity of this assertion, both on statistical and evidence-based grounds. To use IHD risk as an example, Table 2 of the authors’ own subsequent lipid paper (2) suggests that only half of the ultimate IHD risk reduction in LDL lowering is present within the first 2 years. So rather than a 61% reduction by 2 years treatment, it will be nearer 30%. To justify the IHD risk reduction that triple therapy with antihypertensive drugs may bring, the authors, in their hypertension paper,(3) extrapolate from the Prospective Studies Collaboration. However, in this instance no attempt is made to estimate over what period of time (if ever) the treatment will have to be continued before this theoretical reduction in risk is met. Inclusion of homocysteine at all in the analysis seems premature due to the lack of evidence that lowering concentrations is of any benefit in primary prevention of IHD. We have learnt from recent definitive studies investigating antioxidant vitamins and hormone replacement that hypothetical reasons for treatment are not always a guarantee of benefit for real patients. At least the existing evidence for aspirin presented is more compelling, and suggests that the effect on risk reduction is rapid after commencing treatment. Overall, if antihypertensives are assumed to reduce risk at the same rate as statins, and homocysteine is removed from the model due to paucity of evidence, then the reduction in IHD risk after 2 years on the ‘Polypill’ falls from 88% to nearer 66%. Still impressive, admittedly, but if public health policy is to be changed on the basis of this evidence then, in view of this and other errors noted, we need to be sure that this is not only one of the most important papers published by the BMJ in the last 50 years, but also one of the most accurate. References 1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419 2. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423 3. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427 Competing interests: None declared |
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CELIO LEVYMAN,MD,MSc, Staff Neurologist Hospital Israelita Albert Einstein,Unidade Avançada Alphaville,Alameda Purus,105,São Paulo,SP,Brasil, CEP 06454-030
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Polypill, as Wald and Law propose in BMJ, sounds like an esoteric or miraculous marvel of the so-called “alternative” world, and most of us look at this kind of things with skepticism. However, although many rapid responses related to this despise the idea and even mock the subject, it has a strong point assured in the Editorial: the undeveloped countries. I live and work in one of these countries, and a very strange one: Brazil in a large amount of South America, with enormous very poor areas and, in Sao Paulo, my city, and in the Albert Einstein Hospital, my place of work, we have the best of the developed world – is the financial,cultural,research and technological center of all Latin America. However,even in the same city,there are blocks regarding New York City or London, and other like African countries… This is the “beauty” of globalization. But diseases, and cardio and cerebrovascular ones, don’t pay attention to these details, and we have a lot of people with overweight, smoking problems, cholesterol, blood pressure, etc., etc.The academic, evidence-based medicine is offered with primary and secondary prevention interventions, with gold standards, state-of-the art diagnostic and therapeutic weapons – but this is limited to Sao Paulo, Rio de Janeiro and other big cities middle to higher class citizens, with good health plans. The other millions of Brazilians have the public system to take care of them, named here as SUS, and I believe that I don’t have necessity to explain how bad it works. Even in a strange form, a unique pill, resemble such homeopath conducts, without all the absolute result of all investigations, low BP, use statins and aspirin there are not more in the center of the arena, right ?Perhaps folic acid. It is easy to make jokes or very rigid guidelines in relation to “polypill” in UK, USA, Canada, Europe and so. But here, in my real world, there is a lot of practical evidence to support these kinds of ideas. Of course, there are some problems to be solved, like hepatic function and statin, aspirin without gastric protection, interaction of drugs, bioavailability and so on. And the crucial point is one only pill for all kinds of people – but the paper is very important to very countries in the world, and these questions could be answered in a brief time. First world colleagues: do not work like in your countries, be more flexible and please, erase the yellow smile in your faces when someone talk or write about “polypill” or other similar ideas: in my country things could be very sad. Competing interests: None declared |
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J Michael Henk, Hon consultant clinical oncologist Royal Marsden Hospital, Downs Rd Sutton Surrey SM2 5PT
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EDITOR - The outcomes of clinical trials may look impressive when presented as relative risks, but less so when presented as absolute percentages or "numbers required to treat". Would Wald and Law be prepared to present their meta-analyses and estimates of the putative benefit of the combined pill in the latter manner, so that readers can estimate their individual chance of benefitting from taking it? Competing interests: None declared |
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Mark J Garton, Consultant Physician Perth Royal Infirmary, Perth, Scotland PH1 1NX
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EDITOR-Over a conference dinner last week, a respected professor confided that he found the quality of BMJ articles increasingly poor. As an avid reader and occasional contributor I felt obliged to defend the prestigious journal. Sadly the latest issue (28 June 2003) does appear to have wandered into tabloid-style medical journalism, and strays far from its self-declared aim to ‘publish rigorous, accessible and entertaining material that will help doctors and medical students in their daily practice, lifelong learning and career development’. The culprit article is perhaps entertaining but certainly not rigorous. Wald and Law make the spectacular claim that a suitably formulated ‘polypill’ would reduce cardiovascular disease by more than 80%.1 However they fail to take account of several important variables that would significantly degrade the alleged benefits of universal and long-term prescription of their wonder pill. Even if one generously agrees with the authors estimate that 88% of ischaemic heart disease events would be avoided (in reality deferred), the population burden would reduced by a much lesser proportion determined by completeness of healthcare registration,2 the likely response to an invitation to attend a clinic, and longer term issues of adherence and persistence with therapy. Assuming rates of 90%, 80% and 50% for these parameters, the projected benefits would be reduced by about two-thirds. It is also counterintuitive that the entire population should need pharmacologic | |||