Abstract
The June 2003 edition of the British Medical Journal introduced Wald and Law’s concept of a polypill, also known as a fixed-dose combination (FDC) pill. Wald and Law proposed “a strategy to reduce cardiovascular disease by more than 80 %” by simultaneously addressing four cardiovascular risk factors regardless of pretreatment levels in a low-risk population. They stated, “the polypill strategy could largely prevent heart attacks and strokes if taken by everyone aged 55 and older, and everyone with existing cardiovascular disease,” and “widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.” [1] Criticism of the polypill strategy is based on the view that the use of aspirin, statin, and blood pressure (BP)-lowering agents would largely be promoted in a primary prevention setting in a population at a low absolute risk of cardiovascular disease. It was argued that a large proportion of the population would be medicalized unnecessarily, inducing a sense of protection and deflecting attention from healthy behaviors. Although this strategy raised high hopes that a polypill-based treatment could reduce the incidence of atherosclerotic cardiovascular disease exceptionally, the bare truth is that cardiovascular disease is still the major cause of mortality and morbidity worldwide and the polypill has still not largely entered the market.
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References
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326(7404):1419.
Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;113(6):791–8. CIRCULATIONAHA.105.548206 [pii]. doi:10.1161/CIRCULATIONAHA.105.548206 [published Online First: Epub Date].
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(9859):2095–128. doi:10.1016/S0140-6736(12)61728-0 [published Online First: Epub Date].
World Health Organization. Global status report on non-communicable diseases 2010. Geneva: World Health Organization; 2011.
Browne JL, Grobbee DE. Cardiovascular prevention and international health: time for action. Eur J Cardiovasc Prev Rehabil. 2011;18(4):547–9. doi:10.1177/1741826711414116 [published Online First: Epub Date].
Antithrombotic Trialists Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. doi:10.1016/S0140-6736(09)60503-1 [published Online First: Epub Date].
Cholesterol Treatment Trialists Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81. doi:10.1016/S0140-6736(10)61350-5 [published Online First: Epub Date].
Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
Thompson AM, Hu T, Eshelbrenner CL, et al. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305(9):913–22. 305/9/913 [pii]. doi:10.1001/jama.2011.250 [published Online First: Epub Date].
Jackson R, Lawes CM, Bennett DA, et al. Treatment with drugs to lower blood pressure and blood cholesterol based on an individual’s absolute cardiovascular risk. Lancet. 2005;365(9457):434–41. S0140-6736(05)17833-7 [pii]. doi:10.1016/S0140-6736(05)17833-7 [published Online First: Epub Date].
Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.
Kotseva K, Wood D, De Backer G, et al. Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries. Lancet. 2009;373(9667):929–40.
Mendis S, Abegunde D, Yusuf S, et al. WHO study on Prevention of REcurrences of Myocardial Infarction and StrokE (WHO-PREMISE). Bulletin of the World Health Organization. 2005;83(11):820–9. S0042-96862005001100011 [pii]/S0042-96862005001100011 [published Online First: Epub Date].
Gehi AK, Ali S, Na B, et al. Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study. Arch Intern Med. 2007;167(16):1798–803. 167/16/1798 [pii]. doi:10.1001/archinte.167.16.1798 [published Online First: Epub Date].
Newby LK, LaPointe NM, Chen AY, et al. Long-term adherence to evidence-based secondary prevention therapies in coronary artery disease. Circulation. 2006;113(2):203–12. CIRCULATIONAHA.105.505636 [pii]. doi:10.1161/CIRCULATIONAHA.105.505636 [published Online First: Epub Date].
Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.
Mendis S, Fukino K, Cameron A, et al. The availability and affordability of selected essential medicines for chronic diseases in six low- and middle-income countries. Bulletin of the World Health Organization. 2007;85(4):279–88. S0042-96862007000400013. [pii] [published Online First: Epub Date].
World Health Organization. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003.
Gaziano TA, Opie LH, Weinstein MC. Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis. Lancet. 2006;368(9536):679–86. S0140-6736(06)69252-0 [pii]. doi:10.1016/S0140-6736(06)69252-0 [published Online First: Epub Date].
Committee for Medicinal Products for Human Use (CHMP). Guideline on clinical development of fixed combination medicinal products. London: European Medicines Agency; 2009.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry: codevelopment of two or more new investigational drugs for use in combination. Silver Spring: Food and Drug Administration; 2013.
Yusuf S, Pais P, Afzal R, et al. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet. 2009;373(9672):1341–51.
Patel A, Shah T, Shah G, et al. Preservation of bioavailability of ingredients and lack of drug-drug interactions in a novel five-ingredient polypill (polycap): a five-arm phase I crossover trial in healthy volunteers. Am J Cardiovasc Drugs. 2010;10(2):95–103. doi:10.2165/11532170-000000000-00000 [published Online First: Epub Date].
Lafeber M, Grobbee DE, Schrover IM, et al. Comparison of a morning polypill, evening polypill and individual pills on LDL-cholesterol, ambulatory blood pressure and adherence in high-risk patients; a randomized crossover trial. Int J Cardiol. 2014;181C:193–9. doi:10.1016/j.ijcard.2014.11.176 [published Online First: Epub Date].
Malekzadeh F, Marshall T, Pourshams A, et al. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypill’) on cardiovascular risk factors. Int J Clin Pract. 2010;64(9):1220–7. IJCP2412 [pii]. doi:10.1111/j.1742-1241.2010.02412.x [published Online First: Epub Date].
Rodgers A, Patel A, Berwanger O, 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(5):e19857. doi:10.1371/journal.pone.0019857. PONE-D-11-02253 [pii] [published Online First: Epub Date].
Lafeber M, Spiering W, Singh K, et al. The cardiovascular polypill in high-risk patients. Eur J Cardiovasc Prev Rehabil. 2012;19(6):1234–42. doi:10.1177/1741826711428066 [published Online First: Epub Date].
Yusuf S, Pais P, Sigamani A, et al. Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators. Circ Cardiovasc Qual Outcomes. 2012;5(4):463–71. doi:10.1161/CIRCOUTCOMES.111.963637 [published Online First: Epub Date].
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(9):918–29.
Selak V, Elley CR, Bullen C, et al. Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care. BMJ. 2014;348:g3318. doi:10.1136/bmj.g3318 [published Online First: Epub Date].
Patel A, Cass A, Peiris D, et al. A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk. Eur J Prev Cardiol. 2014. doi:10.1177/2047487314530382 [published Online First: Epub Date].
Webster R, Patel A, Billot L, et al. Prospective meta-analysis of trials comparing fixed dose combination based care with usual care in individuals at high cardiovascular risk: the SPACE Collaboration. Int J Cardiol. 2013;170(1):30–5. doi:10.1016/j.ijcard.2013.10.007 [published Online First: Epub Date].
Soliman EZ, Mendis S, Dissanayake WP, et al. A Polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization. Trials. 2011;12:3. 1745-6215-12-3 [pii]. doi:10.1186/1745-6215-12-3 [published Online First: Epub Date]|.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry: fixed dose combinations, co-packaged drug products, and single-entity versions of previously approved antiretrovirals for the treatment of HIV. Rockville: Food and Drug Administration; 2006.
Smith R, McCready T, Yusuf S. Combination therapy to prevent cardiovascular disease: slow progress. JAMA. 2013;309(15):1595–6. doi:10.1001/jama.2013.3180. 1671770 [pii] [published Online First: Epub Date].
Ebrahim S, Beswick A, Burke M, et al. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev. 2006;(4). http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001561/frame.html. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001561.pub2/abstract.
Wald DS, Morris JK, Wald NJ. Randomized Polypill crossover trial in people aged 50 and over. PLoS One. 2012;7(7), e41297. doi:10.1371/journal.pone.0041297 [published Online First: Epub Date].
Wald DS, Law N. Polypill Prevention Programme. Secondary Polypill Prevention Programme. 2013. http://www.polypill.com.
Kmietowicz Z. Polypill inventor puts product online after failing to get backing from industry. BMJ. 2013;346:f3991. doi:10.1136/bmj.f3991 [published Online First: Epub Date].
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Lafeber, M. (2015). The Cardiovascular Polypill in the Prevention of Cardiovascular Disease. In: Banach, M. (eds) Combination Therapy In Dyslipidemia. Adis, Cham. https://doi.org/10.1007/978-3-319-20433-8_14
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