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The use of polypills in cardiovascular disease patients

The introduction of the concept of a polypill, multiple cardioprotective combinations in a single dose, in the early years of this century has led to ample discussion about the benefits and risks of its use in various populations. Only recently results from multiple randomized trials have demonstrated improved adherence to medication and improved risk factor controls in patients with a history of cardiovascular disease and patients at a very high risk of events. Discussion continuous for other indications but the available data support the use of polypill combinations in these categories of patients. While for many years polypills were only available for use in research, recently cardiovascular polypills have become available for use in practice around Europe. The public health implications of polypill use are potentially significant, especially in low-resource settings but also in other settings where adherence rates to secondary prevention are low. This applies to most European countries where guideline based secondary prevention remains suboptimal for many patients as shown in recent surveys.

Adherence to medication has been widely identified as a risk factor to the recurrence of Cardio Vascular Disease (CVD). Good adherence is associated with positive health outcomes and poor adherence to treatment actually increases the likelihood of suffering a recurrent CV event. A recent study further showed that low-risk, intermediate risk and high-risk patients with AMI in the year following discharge, present poor adherence rates to prescribed therapies: 61.5, 57.9 and 45.9 % respectively [1]. Supporting this finding, a previous meta-analysis also demonstrated that compliance with the medication was met only in 66 % of CVD cases [2]. The polypill approach, which combines several medicines that simultaneously control several risk factors or disease mechanisms in a single pill, is one of those strategies that has, in recent years, progressed in the CVD field [3]. The concept was introduced by Wald and Law in 2003, who described a fixed-dose combination strategy, containing six components, and claimed that the administration of this polypill to each individual over 55 years old would reduce the incidence of CVD by more than 80 % [4]. Since then, several polypill concepts have been proposed, including the ‘vaccination approach’, which refers to the use described by Wald and Law, as well as the use in primary and secondary CVD prevention. Polypills are typically defined as combination medication containing at least one blood pressure lowering (often multiple), one lipid lowering drug and frequently an antiplatelet agent. They are also referred to as Fixed Dose Combinations (FDC’s). As with most treatments, the benefits, as well as the drawbacks of the polypill, have been widely discussed. Some argued that the originally proposed estimated risk reduction potential of the polypill could be too optimistic and that many patients would remain undertreated. Concern about potential adverse effects related to some of the polypill’s monocomponents also exist, and it has been argued that side effects from one of the components could lead to discontinuation of treatment. This could then result in the loss of all the benefits of the other components included in the polypill. Nonetheless, despite these concerns, the potential of the polypill to improve the management of CVD risk factors has been recognised by several expert panels, including the WHO and the Combination Pharmacotherapy and Public Health Research Working Group, who consider research in this area an important breakthrough [5]. The currently available evidence shows that the use of polypills (defined as combination medication containing at least one blood pressure lowering and one lipid lowering drug) in patients with established disease or at high risk of developing CVD (i.e. those with established indications for polypill component medications – secondary prevention or high risk primary prevention) improves adherence to CVD preventive medications with consequent improvement in CVD risk factor levels [6]. The focus must now shift to implementing these drugs into clinical practice. Although controversies remain around usage based on single risk factor indications (or mass treatment), use in secondary prevention and high risk primary prevention populations is non-controversial and is the ‘low-hanging fruit’ for polypill usage [7].


  1. Shore S, Jones PG, Maddox TM, Bradley SM, Stolker JM, Arnold SV, et al. Longitudinal persistence with secondary prevention therapies relative to patient risk after myocardial infarction. 2015;101:800–7.
  2. Naderi S, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: Meta-analysis on 376,162 patients. Am J Med. 2012;125(9):882–7.
  3. Fuster V, Gambús F, Patriciello A, Hamrin M, Grobbee DE. The polypill approach - An innovative strategy to improve cardiovascular health in Europe. BMC Pharmacol Toxicol. 2017 Feb 7;18(1):10.
  4. Wald N, Law M. A strategy to reduce cardiovascular disease by more than 80%. 2003;326(7404):1419.
  5. Castellano J, Sanz G, Fuster V. Evolution of the polypill concept and ongoing clinical trials. Can J Cardiol. 2014;30(5):520–6.
  6. Webster R, Patel A, Selak V, et al. Effectiveness of fixed dose combination medication ('polypills') compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries. Int J Cardiol. 2016; 205: 147-56.
  7. Webster R, Castellano JM, Onuma OK. Putting polypills into practice: challenges and lessons learned. Lancet. 2017;389(10073):1066-1074.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The ESC Prevention of Cardiovascular Disease programme is supported by AMGEN, AstraZeneca, Ferrer, and Sanofi and Regeneron in the form of educational grants.

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