A Step Towards a Single Pill for Cardiovascular Disease

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RESEARCH HIGHLIGHTS THERAPY A step towards a single pill for cardiovascular disease prevention A combination pill (Polypill) that receive Polycap (n = 412)—three agents although not significantly different with contains blood-pressure-lowering to lower blood pressure, a statin and Polycap or aspirin alone, did not meet drugs at low doses, plus a statin, aspirin aspirin—or to eight other groups (each the prespecified noninferiority standard. and folic acid could drastically reduce of ~200 individuals) that received only Encouragingly, tolerability of Polycap did cardiovascular disease if taken by certain components of Polycap. Study not seem to be worse than that of its active individuals ≥55 years, irrespective of their drugs were taken for 12 weeks. component drugs. risk factors or history of cardiovascular The results highlight that the effects disease, according to theoretical of a Polypill cannot be assumed to be projections. The Indian Polycap Study Projected reductions in equivalent to the effects of its individual by Yusuf and co-investigators was a cardiovascular disease events components taken separately. Projected phase II, double blind, randomized trial with‘‘ Polycap were 50–60% reductions in cardiovascular disease of one such Polypill: Polycap (Quintapill®, events with Polycap were 50–60%, less Cadila Pharmaceuticals India, India). ’’ than previous estimated effects of a The researchers aimed to examine the Polycap was noninferior to its Polypill, but, nevertheless, substantial. effect of Polycap on blood pressure, lipids, individual components for blood-pressure Further trials will be needed to reveal if heart rate and urinary thromboxane B2 lowering and heart-rate reduction. For a Polypill strategy is safe and effective and to determine whether the effects of example, blood pressure was reduced to long-term. Polycap were noninferior to those of its a similar extent in the Polycap group and Carol Wilson equivalent components. the group assigned to the three blood- The trial, conducted in India, included pressure-lowering agents, with or without Original article Indian Polycap Study (TIPS) et al. Effects 2,053 individuals without cardiovascular aspirin. However, reductions in LDL of a polypill (Polycap) on risk factors in middle-aged disease, aged between 45 and 80 years, cholesterol with Polycap were less than individuals without cardiovascular disease (TIPS): who had one cardiovascular risk factor. those with the statin given alone, and a phase II, double-blind, randomised trial. Lancet 373, 1341–1351 (2009). Participants were randomly allocated to reductions in urinary thromboxane B2, NATURE REVIEWS | ENDOCRINOLOGY VOLUME 5 | AUGUST 2009 | 416 © 2009 Macmillan Publishers Limited. All rights reserved.

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The Polypill and Cardiovascular Disease May Be Appropriate for Secondary, but Perhaps Not for Primary Prevention
Saturday 7 May 2005 BMJ The polypill and cardiovascular disease May be appropriate for secondary, but perhaps not for primary prevention Papers p 1059 he prevention of cardiovascular disease with In the context of primary prevention many drug therapy is well known. Randomised uncertainties remain. Recent evidence concerning the T controlled trials and meta-analyses of trials of differential effect of aspirin in women compared with lipid and blood pressure lowering and antiplatelet men is emerging. While the efficacy of aspirin in men is therapy have established their efficacy in the prevention established,5 the recently completed women’s health of cardiovascular diseases. Wald and Law have proposed study, of low dose aspirin (100 mg every other day) com- that these three treatments, along with folic acid, be pared with placebo, did not produce a reduction in all combined into a “polypill.”1 They propose a combined cause mortality or fatal and non-fatal myocardial infarc- strategy for primary and secondary prevention— tion.6 Although observational evidence favours a targeting all people with pre-existing cardiovascular dis- possible causal association between raised plasma ease (secondary prevention) but more controversially, homocysteine concentrations and cardiovascular dis- targeting all adults aged over 55 (primary prevention) as ease,7 this association has been described as modest; a well. The underlying assumption concerning the efficacy 25% reduction in usual homocysteine concentrations is of this strategy is that the six individual ingredients of the associated with a 11% lower risk of coronary heart polypill (thiazide diuretic, angiotensin converting disease and a 19% lower risk of stroke.8 We have growing enzyme inhibitor, blocker, statin, aspirin, and folic acid) evidence from approaches using mendelian randomisa- when combined together have synergistic treatment tion that the expected effects of the folic acid effects—calculated by multiplying the relative risk reduc- component may not be confirmed.9 Furthermore, a tions on each class of treatment.
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Does the Polypill Improve Patient Adherence Compared to Its Individual Formulations? a Systematic Review
pharmaceutics Review Does the Polypill Improve Patient Adherence Compared to Its Individual Formulations? A Systematic Review Ana Baumgartner 1,2,* , Katarina Drame 1,2, Stijn Geutjens 1,3 and Marja Airaksinen 1 1 Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland; [email protected] (K.D.); [email protected] (S.G.); [email protected] (M.A.) 2 Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia 3 Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium * Correspondence: [email protected] Received: 17 January 2020; Accepted: 20 February 2020; Published: 22 February 2020 Abstract: Many patients, especially those with a high pill burden and multiple chronic illnesses, are less adherent to medication. In medication treatments utilizing polypills, this problem might be diminished since multiple drugs are fused into one formulation and, therefore, the therapy regimen is simplified. This systematic review summarized evidence to assess the effect of polypills on medication adherence. The following databases were searched for articles published between 1 January 2000, and 14 May 2019: PubMed, Web of Science, Cochrane Library, and Scopus. Medication adherence was the only outcome assessed, regardless of the method of measuring it. Sixty-seven original peer-reviewed articles were selected. Adherence to polypill regimens was significantly higher in 56 articles (84%) compared to multiple pill regimens. This finding was also supported by the results of 13 out of 17 selected previously published systematic reviews and meta-analyses dealing with this topic. Adherence can be improved through the formulation of polypills, which is probably why the interest in researching them is growing.
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Polypill Rationale, Evidence, and Progress
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Current and Evolving Landscape for Primary and Secondary Prevention
Current and Evolving Landscape for Primary and Secondary Prevention Cardiovascular Polypill Current and Evolving Landscape for Primary and Secondary Prevention This report was commissioned by the Wellcome Trust and conducted by Globe Life Sciences, and presented at the Third Cardiovascular Combination Pharmacotherapy Global Summit, convened by the World Heart Federation on the 8th June 2016, Mexico City, Mexico. Globe Life Sciences Wellcome Trust World Heart Federation 5, Kew Road 215 Euston Road 32 Rue de Malatrex Surrey, TW9 2PR London NW1 2BE 1201 Geneva United Kingdom United Kingdom Switzerland Tel: +44 (0) 208 334 7070 Tel: +44 (0)20 7611 8545 Tel: (+41 22) 807 03 20 E-mail: [email protected] Email: [email protected] http://www.world-heart-federation.org/ http://www.globelifesciences.com http://www.wellcome.ac.uk 2 3 5 6 7 9 11 20 21 3 Wellcome commissioned Global Life Sciences to assess and report on the current landscape for the polypill in the primary and secondary prevention of cardiovascular diseases (CVD), with the key aim of providing an update on the accumulated evidence in this field. The assessment was conducted based on secondary sources - reviewing the current literature and primary sources – through qualitative interviews with eight key opinion leaders. The scope of the report included commercial, competitor, regulatory, ethical, and clinical dimensions, and an assessment of current hurdles to the adoption of the polypill. The report findings were presented and discussed by the attendees of the Third Cardiovascular Combination Pharmacotherapy Global Summit, Mexico City, 8 June 2016, hosted by the World Heart Federation.
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Editorial the Dilemma of Polypharmacy
Editorial The dilemma of polypharmacy Sarah N Hilmer, Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and University of Sydney Key words: adverse effects, drug interactions, aged, quality use of Polypharmacy is associated with suboptimal prescribing. The medicines. more drugs a patient is exposed to, the more likely they are 2 (Aust Prescr 2008;31:2–3) to be prescribed inappropriately. 'Potentially inappropriate medications' in the elderly include those with sedative or The prevalence of chronic diseases, for which one or more anticholinergic effects and long-acting non-steroidal anti- medicines may be indicated, increases with age. Polypharmacy inflammatory drugs.3 Polypharmacy may occur when additional is usually defined as the use of five or more drugs, including drugs are prescribed to treat the adverse effects of other drugs. prescribed, over-the-counter, and complementary medicines. This is known as the 'prescribing cascade'.4 Other suboptimal It may be a useful prompt for medication review, as it is prescribing associated with polypharmacy includes prescription associated with problems of medication management and of more than one drug in the same class or prescription of a suboptimal prescribing. However, polypharmacy is not a drug that interacts with or is contraindicated in combination clinically useful independent marker of the quality use of with another of the patient's medicines. Ironically, in a study of medicines. The type and dose of medications rather than older patients the probability of under-prescribing – defined as the number of medications determine meaningful clinical lack of an indicated drug when no reason could be found for not outcomes.1 prescribing it – also increased significantly with the number of The more drugs a patient takes, the harder it may be to obtain an drugs prescribed.5 accurate medication history, which impedes informed medication The risk of falls is increased with polypharmacy.
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Polypill. Topic Brief. 2.3.17 Clean
Fixed-dose Combination Therapy for Secondary Prevention of CVD Results of Topic Selection Process & Next Steps The nominator, the Centers for Disease Control and Prevention (CDC) Million Hearts Initiative, is interested in a new AHRQ review on the effectiveness of fixed-dose combination therapy (ie, fixed dosages of aspirin, BP-lowering medication, and cholesterol-lowering medication) on the secondary prevention of cardiovascular disease (CVD). Due to limited original research addressing the key question, the AHRQ Effective Health Care (EHC) Program will not develop a new review on this topic at this time. No further activity on this topic will be undertaken by the AHRQ EHC Program. Topic Brief Topic Name: Centers for Disease Control and Prevention (CDC) Million Hearts Initiative Topic #: 0723 Nomination Date: October 31, 2016 Topic Brief Date: February 2, 2017 Authors: Stephanie Veazie Rose Relevo Mark Helfand Conflict of Interest: None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Summary of Key Findings: • Appropriateness and importance: The nomination is both appropriate and important. Although CVD fixed dose-combination therapy delivered as a single pill (ie, the polypill) has not been approved by the FDA, each of the individual drugs have been approved separately. • Duplication: A new review on this topic would not be duplicative of an existing product. We identified 2 reviews pertinent to the key question; however, these reviews did not include the range of drug delivery options (ie, both as the polypill and separate pills) of interest, nor did they conduct analyses specific to the intervention- comparator pair (fixed-dose combination with aspirin, stain, and ACEI/ARB vs.
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Blood Pressure and Cholesterol Lowering Interventions
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A Protocol for an Economic Evaluation of a Polypill in Patients with Established Or at High Risk of Cardiovascular Disease in a UK NHS Setting: RUPEE (NHS) Study
Open Access Protocol BMJ Open: first published as 10.1136/bmjopen-2016-013063 on 14 March 2018. Downloaded from A protocol for an economic evaluation of a polypill in patients with established or at high risk of cardiovascular disease in a UK NHS setting: RUPEE (NHS) study Catriona Crossan,1,2 Hakim-Moulay Dehbi,3 Hilarie Williams,4 Neil Poulter,4 Anthony Rodgers,5 Stephen Jan,5 Simon Thom,4 Joanne Lord6 To cite: Crossan C, Dehbi H-M, ABSTRACT Strengths and limitations of this study Williams H, et al. A protocol Introduction The ‘Use of a Multi-drug Pill in Reducing for an economic evaluation cardiovascular Events’ (UMPIRE) trial was a randomised ► This paper provides a clear outline of how a model of a polypill in patients with controlled clinical trial evaluating the impact of a established or at high risk for an economic evaluation is developed. polypill strategy on adherence to indicated medication of cardiovascular disease ► Providing an outline of the model structure that in a population with established cardiovascular disease in a UK NHS setting: RUPEE includes details on the underlying epidemiology and (CVD) of or at high risk thereof. The aim of Researching (NHS) study. BMJ Open data inputs will add transparency to the findings of the UMPIRE Processes for Economic Evaluation in the 2018;8:e013063. doi:10.1136/ the RUPEE-NHS study. bmjopen-2016-013063 National Health Service (RUPEE NHS) is to estimate the ► Though the model has been designed to include all potential health economic impact of a polypill strategy for Prepublication history and major adverse and beneficial effects of treatment, ► CVD prevention within the NHS using UMPIRE trial and additional material for this the model structure will not include every potential other relevant data.
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The Polypill Approach – an Innovative Strategy to Improve Cardiovascular
Fuster et al. BMC Pharmacology and Toxicology (2017) 18:10 DOI 10.1186/s40360-016-0102-9 DEBATE Open Access The polypill approach – An innovative strategy to improve cardiovascular health in Europe Valentín Fuster1,2, Francesc Gambús3, Aldo Patriciello4* , Margaretha Hamrin5 and Diederick E. Grobbee6 Abstract Background: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guideline- recommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. Discussion: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. Conclusions: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health.
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Polypill Eligibility and Equivalent Intake in a Swiss Population-Based
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Polypill Improves Adherence but Fails to Win All Scientists' Hearts
NEWS Battle of nerves: Change of heart: New formula: After Syria attacks, Budget cuts loom Techniques in process scientists seek better for the Framingham chemistry enable sarin antidotes Heart Study cheaper HIV drugs 1194 1197 1200 Polypill improves adherence but fails to win all scientists’ hearts Nicholas Wald’s flash of insight came about Such patients with histories of 15 years ago. While recovering from a cardiovascular disease are perfect candidates serious illness at his wife’s family’s house in for the polypill, says Simon Thom, a New York, he watched as his father-in-law cardiologist at Imperial College London who swallowed multiple pills each day to treat led the UMPIRE study. “They’re the low- his cardiovascular disease. “I thought, my hanging fruit of the prevention populace.” goodness, the combined effect of these pills Similar results were previously observed in is very large, but the problem is they should Indian people between the ages of 45 and 80 ensoy / Alamy have started giving them 30 years ago as a without established heart disease but with Ş preventative treatment,” recalls Wald, an a correlated risk factor such as diabetes epidemiologist at the Wolfson Institute (Lancet 373, 1341–1351, 2009). Mehmet of Preventive Medicine at Barts and The What’s still unproven is whether the London School of Medicine and Dentistry improved adherence seen in people taking a Take to heart: One pill for prevention? in the UK. polypill translates to fewer heart attacks and In 2003, a few years after his Eureka strokes in the long run. “I think most people, moment, Wald and his Wolfson colleague myself included, would like to see the data on multiple medications often simply stop Malcolm Law published a statistical analysis that it’s likely to lead to a better [clinical] taking them.
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In the Prevention of Cardiovascular Disease: Rationale and Clinical Data
Review: Clinical Trial Outcomes Polypill (fixed-dose combination) in the prevention of cardiovascular disease: rationale and clinical data Clin. Invest. (2012) 2(12), 1213–1229 Cardiovascular diseases (CVDs) continue to be major contributors of death Kavita Singh1, Abdul Salam2, and disability globally. Control of CVD risk factors has been shown to be Raji Devarajan3, Anushka Patel4 effective in reducing morbidity and mortality both in primary and secondary & Dorairaj Prabhakaran*1,3 prevention settings. Given the cumulative benefits of concurrently controlling 1Center for Chronic Disease Control (CCDC), New multiple CVD risk factors (high blood pressure, dyslipidemia and platelet Delhi, India activity) in individuals at high risk, administration of a polypill consisting of 2The George Institute for Global Health, antihypertensive, antidyslipidemic and antiplatelet agents together could Hyderabad, Andhra Pradesh, India 3COE-CARRS, Public Health Foundation of India simultaneously lower multiple risk factors and applying such a population (PHFI), New Delhi, India risk-reduction strategy has the potential to considerably reduce CVD burden. 4The George Institute for Global Health, Sydney, Furthermore, the availability of an inexpensive generic polypill might improve Australia medication adherence and reduce the evidence–practice gap for individuals *Author for correspondence: who already have an indication for long-term treatment with these agents. A Tel.: +91 11 4342 1957 Fax: +91 11 4342 1975 few clinical trials have provided early evidence about the safety and efficacy E-mail: [email protected] of polypill in primary prevention, however, the result of studies with hard clinical outcomes is some years away. Keywords: aspirin • blood pressure-lowering agents • cardiovascular disease • fixed-dose combination therapy • hyperlipidemia • hypertension • multidrug pill • polypill • statins Cardiovascular diseases (CVDs) are the major contributors of deaths and disability worldwide and are projected to increase in prevalence if the current trend continues [1].
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