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The need to test the theories behind the Polypill: rationale behind the Indian Polycap Study

Nature Clinical Practice Cardiovascular Medicine volume 6, pages 96–97 (2009)Cite this article

Antihypertensive, lipid-lowering and antiplatelet drugs are proven to reduce cardiovascular disease (CVD) events when used in primary and secondary prevention.1,2,3,4,5 Their use is suboptimal, however, owing to factors both at the level of individual patients (cost, multiple dosing and real or perceived adverse effects), and at the health-care-provider level (inadequate time and motivation to emphasize long term adherence). In 2002, Yusuf proposed that use of a four-drug combination consisting of aspirin, a beta-blocker, a statin and an angiotensin-converting-enzyme (ACE) inhibitor for secondary prevention would result in a 75% reduction in patients' cumulative risk of CVD events.6 In an extensive analysis published in 2003, Wald and Law proposed a six-drug combination 'Polypill' that could potentially reduce ischemic heart disease events by 88% and stroke by 80%.7 The combination contained three antihypertensive drugs at half doses (a thiazide, beta-blocker and ACE inhibitor), aspirin, a statin and folic acid. The authors recommended that this pill be taken by all individuals who had a CVD event and by anyone >55 years, without reference to their cardiovascular risk or monitoring treatment to attain specific targets.

These theoretical projections of benefit are based on extrapolations from studies that involved patients with hypertension or hyperlipidemia, and also on an unvalidated assumption that the magnitude of antihypertensive effect of this combination therapy would be large. No data are available on the extent to which this therapy would reduce blood pressure and lipid levels in individuals for whom these parameters were within the normal range. Furthermore, these assumptions do not take into account long-term adherence to the treatment, or its tolerability. We have, therefore, set out to test Wald and Law's hypothesis comprehensively in a multicenter, randomized, controlled, double-blind trial—The Indian Polycap Study (TIPS).

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Acknowledgements

The Indian Polycap Study is sponsored by Cadila Pharmaceuticals India Ltd. The study is registered with www.clinicaltrials.org (NCT00443794) and the Clinical Trials Register of India (CTRI/2008/091/000015, dated: 10-03-2008).

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Authors and Affiliations

  1. D Xavier is Professor and Head of Department, in the Department of Pharmacology, and P Pais is Dean and Professor in the Department of Medicine, A Sigamani is Assistant Professor, at St John's Medical College, Bangalore, India.,

    Denis Xavier, Prem Pais & Alben Sigamani

  2. P Pais is Head of Division and A Sigamani is Trial Manager in the Division of Clinical Trials, D Xavier is the Coordinator, St John's Research Institute, Bangalore.,

    Denis Xavier, Prem Pais & Alben Sigamani

  3. J Pogue and R Azfal are statisticians and S Yusuf is Director of the Population Health Research Institute and Professor of Medicine in the Department of Medicine, McMaster University, Hamilton, ON, Canada.,

    Janice Pogue, Rizwan Afzal & Salim Yusuf

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  1. Denis Xavier
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  6. Salim Yusuf
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on behalf of The Indian Polycap Study (TIPS) Investigators

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Correspondence to Denis Xavier.

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Competing interests

The authors are lead investigators on The Indian Polycap Study, which is registered with www.clinicaltrials.org (NCT00443794) and the Clinical Trials Register of India (CTRI/2008/091/000015, dated: 10-03-2008). The trial sponsor is Cadila Pharmaceuticals India Pvt. Ltd.

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Xavier, D., Pais, P., Sigamani, A. et al. The need to test the theories behind the Polypill: rationale behind the Indian Polycap Study. Nat Rev Cardiol 6, 96–97 (2009). https://doi.org/10.1038/ncpcardio1438

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