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The physiological paradox: reframing the polypill as a vaccine for cardiovascular disease
  1. Michael V Holmes1,
  2. Neeraj Bhala2
  1. 1Faculty of Population Health Sciences, University College London, London, UK
  2. 2Gastroenterology and Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  1. Correspondence to Dr Michael Holmes, Faculty of Population Health Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK; mvholmes{at}

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In his seminal work ‘Sick individuals, sick populations,’1 Geoffrey Rose postulated that reducing the population distribution of a causal risk factor would have a greater effect on population health than targeting only those at high risk (eg, as defined by a threshold value). Population interventions to reduce these risk factors (such as blood pressure) can encompass behavioural modification (eg, reducing dietary salt or smoking cessation) but, for maximum efficacy, should include evidence-based pharmacological treatments. As several established causal risk factors for cardiovascular disease (CVD) exist, each providing a separate target for pharmacological intervention, combining multiple drug treatments into a single pill (a so-called ‘polypill’) maximises efficacy (as originally suggested by Yusuf)2 and helps with drug concordance. This could potentially lead to the use of drugs prescribed to everyone (similar to a vaccine) resulting in potentially huge beneficial effects on population risk of disease.3 However, the concept of a polypill has received controversy, with concerns that it may lead to ‘medicalisation’ of otherwise healthy individuals.4–6 In this article, we set out a basis for why the polypill should be considered as a vital means to prevent vascular disease, and provide populations with the best potential for health, from which all individuals could individually benefit.

Targeting the consequences of epidemiological transition

As nations undergo the epidemiological transition (figure 1),7 the aetiology responsible for the majority proportion of death has changed from pestilence/contagion to non-communicable disease. This is reflected in WHO top causes of death8 (table 1): in low-income countries that have yet to undergo the epidemiological transition, most deaths arise from poor hygiene, overcrowding, absence of antibiotic therapy and/or access to basic healthcare that results in death at an early age predominantly due to contagion. By contrast, the principal causes of death in high-income countries result from non-infectious diseases, such as …

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  • Contributors Both authors devised and wrote the manuscript.

  • Funding This work was supported by UK Medical Research Council grant number G0802432. Dr Bhala was previously supported by a MRC health of the public research fellowship.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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