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Reflections on the regulation of the Polypill

Nature Clinical Practice Cardiovascular Medicine volume 6, pages 94–95 (2009)Cite this article

In a controversial article published in 2003, Wald and Law proposed that a fixed combination of a statin, a beta-blocker, an angiotensin-converting enzyme inhibitor, hydrochlorothiazide, folic acid and aspirin (the 'Polypill') could help to prevent cardiovascular disease.1 The authors estimated that administration of such treatment to all people older than 55 years of age could reduce the total cardiovascular disease burden for society by more than 80%. What they actually advocated was a change in the treatment paradigm from the current, individualized basis of therapy (where treatment is individually tailored and prescribed after a thorough diagnostic procedure) to a standardized intervention given to groups of people who share some common risk factors that indicate a particular therapeutic need. The 'one size fits all' strategy also conflicts with the principle of scientific parsimony—which, in this case, could be interpreted to mean that only patients who actually require treatment should receive it. This rationale was developed to help minimize the risk of potential adverse effects of intervention.

Several things should be considered when generating regulatory recommendations for the development of fixed combinations: official guidelines, the outcome of previous applications and expert scientific advice. European regulatory guidelines for fixed combinations can be found in documents issued by the European Medicines Agency and the Committee for Human Medicinal Products (formerly known as the Committee for Proprietary Medicinal Products).2,3,4,5 These documents are issued to aid the pharmaceutical industry, and give recommendations on what should be included in a drug development plan. The majority of fixed-dose combinations approved in the past few years contain two active components that are both indicated for the treatment of hypertension. These agents are typically an angiotensin-converting enzyme inhibitor and hydrochlorothiazide, and such combinations are not usually associated with regulatory problems. The situation is somewhat different when the proposed combination includes drugs with different indications. At least two such combinations are on the market today—one contains pravastatin and aspirin, the other amlodipine and atorvastatin. The latter combination is approved in countries such as France, where it is indicated for the prevention of cardiovascular events in hypertensive patients who have three additional concomitant cardiovascular risk factors. Approval was mainly based on a large outcome study, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm).6 During the last couple of years two requests have been made for scientific advice with regard to fixed combinations that contain three active components; both these proposals related to combinations for the treatment of patients with hypertension. Multiple substances in fixed combinations will, therefore, soon appear on the market.

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References

  1. Wald NJ and Law MR (2003) A strategy to reduce cardiovascular disease by more than 80%. BMJ 326: 1419

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  2. Committee for Medicinal Products for Human Use (CHMP) and European Medicines Agency (2008) Guideline on the evaluation of medicinal products for cardiovascular disease prevention. [http://www.emea.europa.eu/pdfs/human /ewp/31189007enfin.pdf] (accessed 3 November 2008)

  3. Committee for Medicinal Products for Human Use (CHMP) and European Medicines Agency (2008) Guideline on fixed combination medicinal products. [http://www.emea.europa.eu/pdfs/human/ewp/024095en.pdf] (accessed 3 November 2008)

  4. Committee for Medicinal Products for Human Use (CHMP) and European Medicines Agency (2004) Note for guidance on clinical investigation of medicinal products in the treatment of hypertension. [http://www.emea.europa.eu/pdfs/human/ewp/023895en.pdf] (accessed 3 November 2008)

  5. Committee for Medicinal Products for Human Use (CHMP) and European Medicines Agency (2005) Questions and answers document on the clinical development of fixed combinations of drugs belonging to different therapeutic classes in the field of cardiovascular treatment and prevention. [http://www.emea.europa.eu/pdfs/human/ewp/19158305en.pdf] (accessed 3 November 2008)

  6. Sever PS et al. (2003) Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 361: 1149–1158

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Acknowledgements

The views expressed within this article are the author's own and do not necessarily reflect the views of the Medical Products Agency.

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  1. Medical Products Agency, PO Box 26, SE 751 03 Uppsala, Sweden lennart.forslund@mpa.se

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  1. L Forslund is Head of the Medical Information Unit at the Medical Products Agency, Uppsala, Sweden.,

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Forslund, L. Reflections on the regulation of the Polypill. Nat Rev Cardiol 6, 94–95 (2009). https://doi.org/10.1038/ncpcardio1416

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