Advertisement
Review| Volume 30, ISSUE 5, P520-526, May 2014

Download started.

Ok

Evolution of the Polypill Concept and Ongoing Clinical Trials

Published:March 03, 2014DOI:https://doi.org/10.1016/j.cjca.2014.02.016

      Abstract

      Ischemic heart disease and stroke are the leading causes of death worldwide. What was once thought to be an endemic disease of high income countries has become a global epidemic, as low and middle income countries have adopted Western lifestyles, to the point that noncommunicable diseases are now the main cause of death in these regions, above and beyond communicable diseases, malnutrition, and injury. As a result, a large proportion of individuals at high 10-year risk of a cardiovascular event live in low- and middle-income countries, and the most of all cardiovascular events occur in developing countries. A large amount of evidence supports the use of pharmacological treatment for the prevention of cardiovascular death in this population, including antiplatelet drugs, β-blockers, lipid-lowering agents, and angiotensin-converting enzyme inhibitors, however, the efficacy of cardiovascular event prevention is hampered by several problems, including inadequate prescription of medication, poor adherence to treatment, limited availability of medications, and unaffordable cost of treatment. Here we examine the use of fixed-dose combination therapy, and how this therapy could improve adherence to treatment, reduce the cost, and improve treatment affordability in low-income countries.

      Résumé

      La cardiopathie ischémique et l’accident cérébral vasculaire sont les principales causes de décès à travers le monde. Ce qui était jadis considéré comme une maladie endémique des pays à revenu élevé est devenu une épidémie mondiale, à mesure que les pays à revenu faible et à revenu moyen ont adopté le mode de vie occidentale, si bien que les maladies non transmissibles sont maintenant la cause principale de décès dans ces régions après les maladies transmissibles, la malnutrition et les traumatismes. Par conséquent, une grande proportion d’individus exposés à un risque élevé d’événements cardiovasculaires sur une période de 10 ans vivent dans des pays à faible revenu et à revenu moyen, et la plupart de tous les événements cardiovasculaires apparaissent dans les pays en voie de développement. Un grand nombre de données scientifiques soutiennent l’utilisation du traitement pharmacologique pour prévenir la mortalité cardiovasculaire de cette population, incluant les antiagrégants plaquettaires, les β-bloqueurs, les hypolipidémiants et les inhibiteurs de l’enzyme de conversion de l’angiotensine. Cependant, les divers problèmes, dont les ordonnances de médicaments inadéquates, la mauvaise observance du traitement, la disponibilité limitée des médicaments et le coût inabordable du traitement nuisent à l’efficacité de la prévention des événements cardiovasculaires. Ici, nous examinons l’utilisation du traitement combiné à dose fixe et la manière avec laquelle ce traitement améliorerait l’observance au traitement, réduirait le coût et améliorerait l’accessibilité du traitement dans les pays à faible revenu.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ezzati M.
        • Hoorn S.V.
        • Rodgers A.
        • et al.
        Estimates of global and regional potential health gains from reducing multiple major risk factors.
        Lancet. 2003; 362: 271-280
        • Lozano R.
        • Naghavi M.
        • Foreman K.
        • et al.
        Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease study 2010.
        Lancet. 2012; 380: 2095-2128
        • Yusuf S.
        • Islam S.
        • Chow C.K.
        • 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: 1231-1243
        • Nieuwlaat R.
        • Schwalm J.D.
        • Khatib R.
        • Yusuf S.
        Why are we failing to implement effective therapies in cardiovascular disease?.
        Eur Heart J. 2013; 34: 1262-1269
        • Chapman R.H.
        • Benner J.S.
        • Petrilla A.A.
        • et al.
        Predictors of adherence with antihypertensive and lipid-lowering therapy.
        Arch Intern Med. 2005; 165: 1147-1152
        • Sanz G.
        • Fuster V.
        Polypill and global cardiovascular health strategies.
        Semin Thorac Cardiovasc Surg. 2011; 23: 24-29
        • Yusuf S.
        Two decades of progress in preventing vascular disease.
        Lancet. 2002; 360: 2-3
        • Wald N.J.
        • Law M.R.
        A strategy to reduce cardiovascular disease by more than 80%.
        BMJ. 2003; 326: 1419
        • Sleight P.
        • Pouleur H.
        • Zannad F.
        Benefits, challenges, and registerability of the polypill.
        Eur Heart J. 2006; 27: 1651-1656
        • Sanz G.
        • Fuster V.
        Maximizing therapeutic envelope for prevention of cardiovascular disease: role of polypill.
        Mt Sinai J Med. 2012; 79: 683-688
        • Lonn E.
        • Yusuf S.
        Polypill: the evidence and the promise.
        Curr Opin Lipidol. 2009; 20: 453-459
        • Wald D.S.
        • Wald N.J.
        The polypill in the primary prevention of cardiovascular disease.
        Fund Clin Pharmacol. 2010; 24: 29-35
        • Wald D.S.
        • Morris J.K.
        • Wald N.J.
        Randomized polypill crossover trial in people aged 50 and over.
        PLoS One. 2012; 7: e41297
        • Xavier D.
        • Pais P.
        • Sigamani A.
        • et al.
        The need to test the theories behind the polypill: rationale behind the Indian Polycap Study.
        Nat Clin Pract Cardiovasc Med. 2009; 6: 96-97
        • Malekzadeh F.
        • Marshall T.
        • Pourshams A.
        • et al.
        A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypil’) on cardiovascular risk factors.
        Int J Clin Pract. 2010; 64: 1220-1227
        • Soliman E.Z.
        • Mendis S.
        • Dissanayake W.P.
        • et al.
        A polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization.
        Trials. 2011; 12: 3
        • Group P.C.
        • 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
        • 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. 2013; 310: 918-929
      1. The International Polycap Study 3 (TIPS-3). Available at: http://clinicaltrials.gov/show/NCT01646437. Accessed November 15th, 2013.

      2. Heart Outcomes Prevention Evaluation-3. Available at: http://clinicaltrials.gov/show/NCT00468923. Accessed November 15th, 2013.

      3. Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians Using a Single PolyPill. Available at: http://clinicaltrials.gov/ct2/show/NCT01271985. Accessed November 15th, 2013.

        • Law M.G.
        Cardiovascular complications of HIV: an overview of risk and a novel approach to prevention–the HIV polypill study.
        Curr Opin HIV AIDS. 2006; 1: 482-487
        • Bangalore S.
        • Kamalakkannan G.
        • Parkar S.
        • Messerli F.H.
        Fixed-dose combinations improve medication compliance: a meta-analysis.
        Am J Med. 2007; 120: 713-719
        • Pan F.
        • Chernew M.E.
        • Fendrick A.M.
        Impact of fixed-dose combination drugs on adherence to prescription medications.
        J Gen Int Med. 2008; 23: 611-614
        • Dickson M.
        • Plauschinat C.A.
        Compliance with antihypertensive therapy in the elderly: a comparison of fixed-dose combination amlodipine/benazepril versus component-based free-combination therapy.
        Am J Cardiovasc Drugs. 2008; 8: 45-50
        • Sanz G.
        • Fuster V.
        Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population.
        Nat Clin Pract Cardiovasc Med. 2009; 6: 101-110
        • Fuster V.
        • Sanz G.
        A polypill for secondary prevention: time to move from intellectual debate to action.
        Nat Clin Pract Cardiovasc Med. 2007; 4: 173
        • Thom S.
        • Field J.
        • Poulter N.
        • et al.
        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.
        Eur J Prev Cardiol. 2014; 21: 252-261
        • Sanz G.
        • Fuster V.
        • Guzman L.
        • et al.
        The fixed-dose combination drug for secondary cardiovascular prevention project: improving equitable access and adherence to secondary cardiovascular prevention with a fixed-dose combination drug. Study design and objectives.
        Am Heart J. 2011; 162: 811-817.e1
        • Narayan K.M.
        • Mensah G.A.
        • Sorensen S.
        • et al.
        Combination pharmacotherapy for cardiovascular disease prevention: threat or opportunity for public health?.
        Am J Prev Med. 2005; 29: 134-138
        • Antithrombotic Trialists' Collaboration
        Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324: 71-86
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • et al.
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366: 1267-1278
        • Dagenais G.R.
        • Pogue J.
        • Fox K.
        • Simoons M.L.
        • Yusuf S.
        Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials.
        Lancet. 2006; 368: 581-588
        • Yusuf S.
        • Peto R.
        • Lewis J.
        • Collins R.
        • Sleight P.
        Beta blockade during and after myocardial infarction: an overview of the randomized trials.
        Prog Cardiovasc Dis. 1985; 27: 335-371
        • Muntner P.
        • Mann D.
        • Wildman R.P.
        • et al.
        Projected impact of polypill use among us adults: medication use, cardiovascular risk reduction, and side effects.
        Am Heart J. 2011; 161: 719-725
        • Gaziano T.A.
        • Opie L.H.
        • Weinstein M.C.
        Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis.
        Lancet. 2006; 368: 679-686
        • Lim S.S.
        • Gaziano T.A.
        • 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: 2054-2062