Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe

Abstract

The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward, yet in practice the adoption of such measures is disappointingly low, plus there is wide international variation in preventive therapies.

Several barriers might explain this shortfall and variation, but the simplicity and economy of a polypill-based strategy might overcome some barriers. The ‘Use of a Multidrug Pill In Reducing cardiovascular Events’ (UMPIRE) trial assesses whether a polypill strategy (by combining aspirin, a statin and two blood pressure lowering agents) would improve adherence to guideline-indicated therapies and would lower both blood pressure and cholesterol, in people with established cardiovascular disease. UMPIRE, running in India and three European countries (England, Ireland and the Netherlands), is an open, randomised, controlled trial designed to include 1000 participants in India and 1000 in Europe, with a followup of 12–24 months. Participants were randomised to one of two versions of the polypill or relegated to usual care. The primary study outcomes were the self-reported use of aspirin, a statin and at least two blood pressure lowering agents; as well as changes in blood pressure and cholesterol. Secondary outcomes included: any cardiovascular events, reasons for stopping medications, serious adverse events and perceived changes in quality of life. Interpretation of the study data will be enhanced by health, economic and process-related evaluations. UMPIRE is registered with the European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250. The trial was part of the ‘Single Pill Against Cardiovascular Events (SPACE)’ collaboration, which encompasses the ‘IMProving Adherence using Combination Therapy (IMPACT)’ and ‘Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)’ trials.

Keywords

Polypill cardiovascular disease prevention adherence multicentre study combination therapy

Get full access to this article

View all access options for this article.

References

Tunstall-Pedoe H. The decline in coronary heart disease; did it fall or was it pushed? BMJ 2012; 344: d7809.

World Health Organisation. The World Medicines Situation; World pharmaceutical sales and consumption 2004, http://apps.who.int/medicinedocs/en/d/Js6160e/6.html (2004, accessed 10 May 2012).

Perkovic

Huxley

. The burden of blood pressure-related disease: A neglected priority for global health. Hypertens 2007; 50: 991–997.

World Health Organisation, World Heart Federation and World Stroke Organization. Global Atlas on cardiovascular disease prevention and control, http://www.who.int/cardiovascular_diseases/publications/atlas_cvd/en/index.html (2011, accessed 10 May 2012).

Yusuf

Islam

Chow

. 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: 1231–1243.

Mendis

Fukino

Cameron

. The availability and affordability of selected essential medicines for chronic diseases in six low- and middle-income countries. BullWHO 2007; 85: 279–288.

Niens LM, Cameron A, Van de Poel E, et al. Quantifying the impoverishing effects of purchasing medicines: A cross-country comparison of the affordability of medicines in the developing world. PLoS Med 2010; 7: 10.1371/journal.pmed.1000333.

Claxton

Cramer

Pierce

. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296–1310.

World Health Organisation. Adherence to long-term therapies; evidence for action, http://www.who.int/chp/knowledge/publications/adherence_full_report.pdf (2003, accessed 10 May 2012).

10.

Lafeber M, Spiering W, Singh K, et al. The cardiovascular polypill in high-risk patients. Eur Journal Cardiovasc Prev Rehab 2011; epub October, 2011 (http://www.ncbi.nlm.nih.gov/pubmed/22019908).

11.

Liu

Patel

Brown

. Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP) study: A randomised controlled trial of a polypill-based strategy amongst indigenous and non indigenous people at high cardiovascular risk. BMC Pub Health 2010; 10: 458–458.

12.

Selak

Elley

Crengle

. IMProving Adherence using Combination Therapy (IMPACT): Design and protocol of a randomised controlled trial in primary care. Contemp Clin Trials 2011; 32: 909–915.

13.

Anderson

Wilson

Odell

. An updated coronary risk profile. A statement for health professionals. Circul 1991; 83: 356–362.

14.

New Zealand Guidelines Group. Evidence-based best practice guideline, the assessment and management of cardiovascular risk, http://www.nzgg.org.nz/ (2003, accessed 10 May 2012).

15.

Yusuf

Reddy

Ounpuu

. Global burden of cardiovascular diseases: Part I: General considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001; 104: 2746–2753.

16.

Wattanakit

Folsom

Chambless

. Risk factors for cardiovascular event recurrence in the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J 2005; 149: 606–612.

17.

Yusuf

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

18.

Wald

Law

. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419–1419.

19.

World Health Organisation. WHO model list of essential medicines, http://whqlibdoc.who.int/hq/2011/a95053_eng.pdf (2011, accessed 10 May 2012).

20.

Gehi

Ali

. Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: The heart and soul study. Arch Int Med 2007; 167: 1798–1803.

21.

Bangalore

Kamalakkannan

Parkar

. Fixed-dose combinations improve medication compliance: A meta-analysis. Am J Med 2007; 120: 713–719.

22.

Gupta

Arshad

Poulter

. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: A meta-analysis. Hypertens 2010; 55: 399–407.

23.

Choudhry

Avorn

Glynn

. Full coverage for preventive medications after myocardial infarction. NEJM 2011; 365: 2088–2097.

24.

Grover

Citro

. India: Access to affordable drugs and the right to health. Lancet 2011; 377: 976–977.

25.

Bonita

Beaglehole

. Stroke prevention in poor countries: Time for action. Stroke 2007; 38: 2871–2872.

26.

Beaglehole

Ebrahim

Reddy

. Prevention of chronic diseases: A call to action. Lancet 2007; 370: 2152–2157.

27.

Beaglehole

Bonita

Horton

. Priority actions for the non-communicable disease crisis. Lancet 2011; 377: 1438–1447.

28.

Folsom

Yatsuya

Nettleton

. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol 2011; 57: 1690–1696.

29.

Mozaffarian

. Achieving cardiovascular health: A bleak outlook or tremendous potential? Je Am Coll Cardiol 2011; 57: 1697–1699.

30.

Narayan

Ali

Koplan

. Global noncommunicable diseases–where worlds meet. NEJM 2010; 363: 1196–1198.

31.

World Health Organisation. Secondary prevention of non-communicable disease in low and middle income countries through community-based and health service interventions; Wellcome Trust meeting, http://whqlibdoc.who.int/hq/2002/WHO_MPN_CVD_2002.01.pdf (2002, accessed 10 May 2012).

32.

Lim

Gaziano

Gakidou

. Prevention of cardiovascular disease in high-risk individuals in low-income and middle-income countries: Health effects and costs. Lancet 2007; 370: 2054–2062.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.07 MB