Skip to main content

Advertisement

Log in

Polypill: Progress and Challenges to Global Use—Update on the Trials and Policy Implementation

  • Public Health Policy (TA Gaziano, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality globally. Most people with cardiovascular disease do not take long-term cholesterol-lowering, anti-platelet and blood pressure-lowering medications despite proven benefits. Fixed-dose combination pills (‘polypills’) have been shown to improve adherence to these recommended medications with corresponding improvements in risk factors such as blood pressure and low-density lipoprotein (LDL) cholesterol. Among patients not taking the full complement of recommended CVD preventive therapies, use of a polypill-based strategy (i.e. initiating treatment with single-pill combination medication then titrating further therapy as needed) has large potential benefits in reducing global morbidity and mortality. Despite this, few polypills are available on the market due to market failure in the funding of research and development for affordable non-communicable disease medicines. Additionally, defining a path to market has been problematic in that fixed-dose combinations with multiple different drug classes included are quite novel, and regulatory processes to review these types of applications are not well established. Despite these delays, progress is slowly being made.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.

    Article  PubMed  Google Scholar 

  2. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.

    Article  CAS  PubMed  Google Scholar 

  4. Kotseva K, Wood D, De Backer G, et al. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil. 2009;16:121–37.

    Article  PubMed  Google Scholar 

  5. Kumar A, Fonarow GC, Eagle KA, et al. Regional and practice variation in adherence to guideline recommendations for secondary and primary prevention among outpatients with atherothrombosis or risk factors in the United States: a report from the REACH registry. Crit Pathways Cardiol. 2009;8:104–11.

    Article  Google Scholar 

  6. Webster RJ, Heeley EL, Peiris DP, et al. Gaps in cardiovascular disease risk management in Australian general practice. Med J Austr. 2009;191:324–9.

    Google Scholar 

  7. Mendis S, Abegunde D, Yusuf S, et al. WHO study on prevention of recurrences of myocardial infarction and stroke (WHO-PREMISE). B World Health Organ. 2005;83:820–9.

    Google Scholar 

  8. Sharma KK, Gupta R, Agrawal A, et al. Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India. Vasc Health Risk Manage. 2009;5:1007–14.

    Google Scholar 

  9. Yusuf S, Islam S, Chow CK, et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE study): a prospective epidemiological survey. Lancet. 2011;378:1231–43.

    Article  PubMed  Google Scholar 

  10. World Health Organization. Secondary prevention of non-communicable disease in low and middle income countries through community-based and health service interventions. World Health Organization-Wellcome trust meeting report. Geneva; 2002.

  11. Yusuf S. Two decades of progress in preventing vascular disease. Lancet. 2002;360:2–3.

    Article  PubMed  Google Scholar 

  12. World Health Organization. The World Health Report 2002: Reducing risks, promoting healthy life. Edited by: World Health Organization. Geneva; 2002.

  13. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80 %. Br Med J. 2003;326:1419.

    Article  CAS  Google Scholar 

  14. Malekzadeh F, Marshall T, Pourshams A, et al. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypill’) on cardiovascular risk factors. Int J Clin Pract. 2010;64:1220–7.

    Article  CAS  PubMed  Google Scholar 

  15. Pill Collaborative Group, Rodgers A, Patel A, et al. An international randomised placebo-controlled trial of a four-component combination pill (“polypill”) in people with raised cardiovascular risk. PLoS One. 2011;6:e19857.

    Article  PubMed Central  Google Scholar 

  16. Wald DS, Morris JK, Wald NJ. Randomized polypill crossover trial in people aged 50 and over. PLoS One. 2012;7:e41297. Results from a 12 week cross over RCT of polypill vs placebo in primary prevention.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Yusuf S, Pais P, Sigamani A, et al. Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (Polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators. Circulation. Cardiovasc Qual Outcome. 2012;5:463–71. Showed incremental improvement in risk factor reduction when full-dose polypill was used in patients at high CVD risk compared to low-dose polypill.

    Article  Google Scholar 

  18. Indian Polycap S, Yusuf S, Pais P, et al. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial.[see comment]. Lancet. 2009;373:1341–51.

    Article  Google Scholar 

  19. Lonn E, Bosch J, Teo KK, et al. The polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions. Circulation. 2010;122:2078–88.

    Article  PubMed  Google Scholar 

  20. PolyIran. Available at http://clinicaltrials.gov/ct2/show/NCT01271985?term=polyiran&rank=1. Accessed July 2013

  21. HOPE 3. Available at http://clinicaltrials.gov/ct2/show/NCT00468923?term=hope+3&rank=1. Accessed July 2013

  22. TIPS 3. Available at http://clinicaltrials.gov/ct2/show/NCT01646437?term=tips+3&rank=1. Accessed July 2013

  23. Thom S, Poulter N, Field J, et al. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA J Am Med Assoc. 2013;310:918–29. First large scale RCT of polypill vs usual care in secondary prevention of 2004 patients from Western Europe and India. Showed improvement in adherence, systolic blood pressure and LDL-cholesterol.

    Article  CAS  Google Scholar 

  24. Patel A, Cass A, Peiris D et al. A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk. Eur J Prevent Cardiol. 2014. Randomised trial of polypill vs usual care in 623 Australian patients, including 50 % indigenous participants. Showed improvement in adherence to recommended CVD therapy.

  25. Selak V, Elley CR, Bullen C et al. Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care. BMJ 2014;348. Randomised trial of polypill vs usual care in 513 New Zealand patients, including 50 % Maori participants. Showed improvement in adherence to recommended CVD therapy.

  26. Castellano JM, Sanz G, Penalvo JL et al. A polypill strategy to improve adherence: results from FOCUS (Fixed-dose Combination Drug for Secondary Cardiovascular Prevention) Project. J Am Coll Cardiol. 2014. Randomised trial of polypill vs components taken as individual medications. Showed improvement in adherence.

  27. HOPE 4. Available at http://clinicaltrials.gov/ct2/show/NCT01826019?term=hope+4&rank=1. Accessed 10 October 2014

  28. Virdee SK, Greenfield SM, Fletcher K, et al. Would primary healthcare professionals prescribe a polypill to manage cardiovascular risk? A qualitative interview study. BMJ Open. 2013. doi:10.1136/bmjopen-2012-002498.

    Google Scholar 

  29. Viera AJ, Sheridan SL, Edwards T, et al. Acceptance of a polypill approach to prevent cardiovascular disease among a sample of U.S. physicians. Prev Med. 2011;52:10–5.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Steinberg G. Polypills: a new solution to help improve medication adherence. 2015. Available at https://news.aetna.com//polypills-new-solution-help-improve-medication-adherence/. Accessed 19th June 2015

  31. Lim SS, Gaziano TA, Gakidou E, et al. Prevention of cardiovascular disease in high-risk individuals in low-income and middle-income countries: health effects and costs. Lancet. 2007;370:2054–62.

    Article  PubMed  Google Scholar 

  32. World Health Organisation. Global action plan for the prevention and control of noncommunicable diseases. Geneva: World Health Organization; 2013.

    Google Scholar 

Download references

Acknowledgements

The authors have received grants from several research charities and national funding agencies for research on cardiovascular fixed-dose combination medications and from Dr. Reddys Ltd for co-ordination of the SPACE programme. The George Institute for Global Health obtained an exclusive global license in Dec 2012 for the fixed-dose combinations used in the SPACE trials following a decision by Dr. Reddy’s Ltd not to proceed with taking the products to market because of uncertainty in regulatory requirements.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ruth Webster.

Ethics declarations

Conflict of Interest

Anthony Rodgers is supported by an NHMRC Principle Research Fellowship. Ruth Webster is supported by a Heart Foundation of Australia post-doctoral fellowship.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Public Health Policy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Webster, R., Rodgers, A. Polypill: Progress and Challenges to Global Use—Update on the Trials and Policy Implementation. Curr Cardiol Rep 17, 121 (2015). https://doi.org/10.1007/s11886-015-0673-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-015-0673-x

Keywords

Navigation