Polypill to help combat CVD

Current situation - There has been great interest in the possible introduction of the 'polypill' to reduce cardiovascular diseases in the UK.

  • The polypill concept was proposed by Professors Wald and Law (BMJ 2003; 326: 1,419). They suggested six ingredients: a statin, aspirin, folic acid and three antihypertensives (a thiazide, a beta-blocker, and an ACE inhibitor), each at half dose. They proposed the polypill as secondary prevention and also as primary prevention for all adults over 55 years.
  • The combination would prevent heart disease and stroke by reducing four different risk factors, BP, lipids, homocysteine and platelet function. They calculated that CHD would be reduced by 88 per cent and strokes by 80 per cent.

What is the evidence?

  • An analysis of the individual and combined effects of three of the polypill ingredients has provided support for the synergistic action of the polypill (BMJ 2005; 330: 1,059-63).
  • Supplements combining folic acid and vitamins B6 and B12, which can be taken to reduce homocysteine levels, did not reduce the risk of CHD (NEJM 2006; 354: 1,629) or venous thromboembolism in another trial (Ann Intern Med 2007; 146: 761-7). - Although folic acid reduces plasma homocysteine, a meta-analysis of randomised trials found that it did not reduce the risk of cardiovascular disease in patients with pre-existing vascular or renal disease (JAMA 2006; 296: 2,720-6).
  • One study has shown that giving the polypill to everyone over 60 years would actually produce the greatest health gains (J Epidemiol Community Health 2006; 60: 213-7).
  • An analysis of relevant studies showed that the trials alone provide weak evidence for folic acid and that they are too small to be conclusive. But on the basis of all the evidence, the authors take the view that there is now sufficient evidence to support lowering homocysteine concentrations to reduce cardiovascular disease risk (BMJ 2006; 333: 1,114-7).
  • A meta-analysis of trials to assess the efficacy of folic acid supplementation in the prevention of stroke showed that folic acid supplementation reduced the risk of stroke by 18 per cent. A beneficial effect was seen in trials with a treatment duration of more than 36 months and no history of stroke (Lancet 2007; 369: 1,876-82).

Implications for practice

  • Trials would be needed before it would be possible to give the polypill to whole populations for primary prevention without any screening.
  • There is some concern of 'medicalising' a healthy population by using the polypill for primary prevention in middle-aged and older individuals (Ann Intern Med 2005; 142: 467-8).
  • There are many factors that need to be considered regarding the risks of giving such a combination of medications.


  • The polypill consists of a statin, aspirin, folic acid and three antihypertensives.
  • The polypill should not be an alternative to a healthy lifestyle.
  • Further trials are needed to support the polypill in primary prevention.
Dr Louise Newson is a GP in the West Midlands and author of 'Hot Topics for MRCGP and General Practitioners' Pas Test 2006

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