Review
Evolution of the Polypill Concept and Ongoing Clinical Trials

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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.

Section snippets

The Polypill: Evolution of a Concept

Fixed-dose combination (FDC) drugs have been present in the therapeutic armamentarium for several decades, particularly for the treatment of hypertension. However, its use declined, mainly because the impossibility of adapting treatment to each patient's needs. At the beginning of the present century, several authors proposed the use of FDCs for CVD prevention.7 The term, ‘polypill,’ was coined by Wald and Law in a seminal paper published in 2003,8 who claimed that a FDC comprised of 6

Rationale for the Components of the Polypill

Aspirin, statins, ACE inhibitors, and β-blockers are routinely administered in all patients recovering from an acute MI who do not have contraindications to these drugs. Data from the Antiplatelet Trialists' Collaboration demonstrated that after an MI, for every 1000 patients treated with aspirin, 18 nonfatal infarctions, 5 nonfatal strokes, and 14 vascular deaths are prevented.31 The Cholesterol Treatment Trialists' Collaboration analyzed the efficacy and safety of statins in 14 randomized

Potential Benefit of a Polypill in CVD Prevention

The projected effect of polypill use among US adults has been explored by Muntner et al.35 Using population-based survey data, they found that 67.6 million US adults would be eligible if the polypill were given to everyone at least 55 years of age, and 15.4 million would be eligible if the pill were given to those with a history of CVD. By multiplying estimated risk reductions, they estimated this could reduce the 10-year incidence of coronary heart disease and stroke by 44% and 37%,

Conclusions

The deteriorating health of the population and the increasing prevalence of chronic diseases is a global problem with causes that are multifactorial and complex. Interventions to promote healthy lifestyles have proven to be effective, and national campaigns and health policies can make an important contribution to controlling risk factor levels in the general population. However, the evolution from a global landscape where death and morbidity are now dominated by CVD and other noncommunicable

Disclosures

The authors have no conflicts of interest to disclose.

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  • Cited by (17)

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      In this scenario, the healthcare systems of LMIC, which do not have the means to ensure adequate patient services, can adopt the polypill strategy because patients should be able to manage it autonomously. In settings with fewer resources, a polypill strategy is potentially critical considering that a 1-month supply of standard generic secondary prevention medications can cost a government worker in a low-income country approximately 1.6 to 18.4 days of work wages (40). From a business model point of view, one of the major appeals of an FDC polypill is the use of low-cost mature drugs in an efficient manner.

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      We can argue theory as much as we want, but ultimately the value of the polypill approach will be determined by prospective randomized clinical trials assessing its effects on clinically important hard end points. Several such trials are under way—the interested reader is referred to a detailed review article discussing them in this issue of the Canadian Journal of Cardiology.12 Following on Wald and Law's seminal thesis now more than a decade ago, we have ample evidence that a multiple-drug (poly) pill is a theoretically and practically highly effective approach to primary prevention (for high-risk individuals), and for secondary prevention.

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