Abstract
Primary prevention is recognized as the “holy grail” in combating the global burden of cardiovascular diseases (CVD) and will play an important role in achieving World Heart Federation’s goal of reducing premature mortality from CVD by 25 % by 2025. Current primary prevention strategies, which focus on treating cardiovascular risk factors to set targets and individualizing treatments, are impractical for wide application at a population level. The “polypill” hypothesis of Wald and Law (2003) – that treating all people above 55 years of age with a fixed-dose combination of medication targeting at least two risk factors in a single pill could reduce CVD by 80 % – has generated both great hope and controversy. The concept is based on the premise that risk factors tend to cluster and that the level of risk is continuous with no inflection point. In addition, a once-a-day pill will likely improve patient medication adherence. Proof-of-concept trials have been undertaken and these have demonstrated initial successes and a few setbacks. Based on evidence from these studies, the polypill has been approved by regulatory agencies in some countries for secondary prevention. Large phase 3 primary prevention trials evaluating the efficacy of the polypill on clinical outcomes are underway. Today, there are at least five formulations of the polypill available. If the pivotal phase 3 trials prove to be successful in reducing clinical outcomes, a combination of the polypill strategy combined with a reorientation of the health system for effective delivery of the polypill could prove to be the most effective weapon in the armamentarium to achieve primary CVD prevention and reduce premature mortality from CVD.
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References
World Health Organization. Global action plan for the prevention and control of noncommunicable disease 2013–2020. Geneva: WHO; 2013. p. 7.
Tunstall-Pedoe H, Kuulasmaa K, Mähönen M, Tolonen H, Ruokokoski E, Amouyel P, for the WHO MONICA (monitoring trends and determinants in cardiovascular disease) Project. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA Project populations. Lancet. 1999;353:1547–57.
McManus DD, Gore J, Yarzebski J, Spencer F, Lessard D, Goldberg RJ. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am J Med. 2011;124:40–7.
Feigin VL, Lawes CMM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population based studies of incidence, prevalence and case-fatality in the late 20th century. Lancet Neurol. 2003;2:43–53.
Xavier D, O’Donnell M, Pais P, et al. The Indian Stroke Registry (INSPIRE). In: Proceedings of the World Congress of Cardiology, Melbourne, 2014.
Montalescot G, Dallongeville J, Van Belle E, et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J. 2007;28:1409.
Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke. 1994;25:333–7.
Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS, Gupta R, Joshi P, Kerkar P, Thanikachalam S, Haridas KK, Jaison TM, Naik S, Maity AK, Yusuf S, on behalf of the CREATE registry investigators. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet. 2008;371:1435–42.
de Cates AN, Farr MRB, Wright N, Jarvis MC, Rees K, Ebrahim S, Huffman. Fixed-dose combination therapy for the prevention of cardiovascular disease (Review). Cochrane Libr. Published Online: 16 Apr 2014. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009868.pub2/pdf. Accessed 23 Aug 2014.
Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, on behalf of the INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.
O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S, Pais P, McQueen M, Mondo C, Damasceno A, Lopez-Jaramillo P, Hankey GJ, Dans AL, Yusoff K, Truelsen T, Diener H, Sacco RL, Ryglewicz D, Czlonkowska A, Weimar C, Wang X, Yusuf S, on behalf of the INTERSTROKE investigators. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112–23.
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.
Rapsomaniki E, Timmis A, George J, Pujades-Rodriguez M, Shah AD, Denaxas S, White IA, Caulfield MJ, Deanfield JE, Smeeth L, Williams B, Hingorani A, Hemingway H. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people. Lancet. 2014;383:1899–911.
Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–35.
Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.
Gupta R, Deedwania PC, Achari A, Bhansali A, Gupta BK, Gupta A, Mahanta TG, Asirvatham AT, Gupta S, Maheshwari A, Saboo B, Jali MV, Singh J, Guptha S, Sharma KK. Normotension, prehypertension, and hypertension in urban middle-class subjects in India: prevalence, awareness, treatment, and control. Am J Hypertens. 2013;26:83–94. doi:10.1093/ajh/hps013.
Kannel WB. Risk stratification in hypertension: new insights from the Framingham study. Am J Hypertens. 2000;13(S1):3S–10. doi:10.1016/S0895-7061(99)00252-6.
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419–24.
Rose G. Strategy of prevention: lessons from cardiovascular disease. BMJ. 1981;282:1847–51.
Stone NJ, Robinson J, Lichtenstein AH, BaireyMerz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC, Watson K, Wilson PWF. ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013. doi:10.1161/01.cir.0000437738.63853.7a. Accessed 26 Aug 2014.
Mozaffarian D, Afshin A, Benowitz NL, Bittner V, Daniels SR, Franch HA, Jacobs DR, Kraus WE, Kris-Etherton PM, Krummel DA, Popkin BM, Whitsel LP, Zakai NA, American Heart Association Council on Epidemiology and Prevention, Council on Nutrition, Physical Activity and Metabolism, Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on the Kidney in Cardiovascular Disease, Council on Peripheral Vascular Disease, Advocacy Coordinating Committee. Population approaches to improve diet, physical activity, and smoking habits: a scientific statement from the American Heart Association. Circulation. 2012;126:1514–63.
Zatonski WA, McMichael AJ, Powles JW. Ecological study of reasons for sharp decline in mortality from ischaemic heart disease in Poland since 1991. BMJ. 1998;316:1047–51.
Vartiainen E, Puska P, Pekkanen J, Tuomilehto J, Jousilahti P. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ. 1994;309:23–7.
Yusuf S, Islam S, Chow CK, Rangarajan S, Dagenais G, Diaz R, Gupta R, Kelishadi R, Iqbal R, Avezum A, Kruger A, Kutty R, Lanas F, Lisheng L, Wei L, Lopez-Jaramillo P, Oguz A, Rahman O, Swidan H, Yusoff K, Zatonski W, Rosengren A, Teo AA, on behalf of the Prospective Urban Rural Epidemiology (PURE) Study Investigators. 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;378:1231–43.
Kotseva K, Wood D, De Backer G, De Bacquer D, Pyo¨ra¨la¨ K, Keil U, EUROASPIRE Study Group. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil. 2009;16:121–37.
Ebrahim S, Beswick A, Burke M, Davey SG. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev. 2006;4:CD001561.
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. doi:10.1136/bmj.b1665.
Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003;326:1423.
Halsey CR, Lewington S, Lonn E, Armitage J, Manson JE, Bønaa KH, Spence JD, Nygård O, Jamison R, Gaziano JM, Guarino P, Bennett D, Mir F, Peto R, Collins R, for the B-Vitamin Treatment Trialists’Collaboration. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: metaanalysis of 8 randomized trials involving 37,485 individuals. Arch Intern Med. 2010;170:1622–31.
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A, Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.
Patel A, Shah T, Shah G, Jha V, Ghosh C, Desai J, Khamar B, Chakraborthy BS. Preservation of bioavailability of ingredients and lack of drug- drug interaction in a novel five ingredient polypill (Polycap™). Am J Cardiovasc Drugs. 2010;10:96–103.
Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J, Sigamani A, Mohan V, Gupta R, Thomas N. The Indian Polycap Study (TIPS). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomized trial. Lancet. 2009;373:1341–51.
Group PC, Rodgers A, Patel A, Berwanga O, Bots M, Grimm R, Grobbee DE, Jackson R, Neal B, Neaton J, Poulter N, Rafter N, Raju PK, Reddy S, Thom S, Vander Hoon S, Webster R. An international randomized placebo-controlled trial of a four component combination pill (‘polypill’) in people with raised cardiovascular risk. PLoS One. 2011;6:e 19857.
Malekzadeh F, Marshall T, Pourshams A, Gharravi M, Aslani A, Nateghi A, Rastergarpanah M, Khoshnia M, Semnani S, Salahi R, Thomas GN, Larijani B, Cheng KK, Malekzadeh R. A pilot double blind randomized placebo controlled trial of the effects of fixed dose combination therapy (‘polypill’) on cardiovascular risk factors. Int J Clin Pract. 2010;64:1220–7.
Yusuf S, Pais P, Sigamani A, Xavier D, Afzal R, Gao P, Teo KK. 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;5:463–71.
TIPS 3 Trial. ClinicalTrials.gov Identifier: NCT01646437.
HOPE 3 Trial. ClinicalTrials.gov Identifier: NCT00468923.
Patel A, Cass A, Peiris D, Usherwood T, Brown A, Jan S, Neal B, Hillis GS, Rafter N, Tonkin A, Webster R, Billot L, Bompoint S, Burch C, Burke H, Hayman N, Molanus B, Reid CM, Shiel L, Togni S, Rodgers A for the Kanyini Guidelines Adherence with the Polypill (Kanyini GAP) Collaboration. 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. 10.1177/2047487314530382, first published on 27 Mar 2014.
Thom S, Poulter N, Field J, Patel A, Prabhakaran D, Stanton A, Grobbee DE, Bots ML, Reddy KS, Cidambi R, Bompoint S, Billot L, Rodgers A, for the UMPIRE Collaborative Group. 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;310:918–29. doi:10.1001/jama.2013.277064.
de Cates AN, Farr MRB, Wright N, Jarvis MC, Rees K, Ebrahim S, Huffman MD. Fixed-dose combination therapy for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2014;(4):CD009868. doi:10.1002/14651858.CD009868.pub2.Cochrane review.
Webster R, Patel A, Billot L, Cass A, Burch C, Neal B, Usherwood T, Thom S, Poulter N, Stanton A, Bots ML, Grobbee DE, Prabhakaran D, Reddy KS, Field J, Bullen C, Raina Elley C, Selak V, Rafter N, Wadham A, Berwanger O, Rodgers A, on behalf of the SPACE Collaboration. 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;170:30–5.
HOPE 4 trial. ClinicalTrials.gov Identifier: NCT 01826019.
Smith R. The most important BMJ for 50 years? BMJ. 2003;326. http://dx.doi.org/10.1136/bmj.326.7404.0-f.
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Pais, P., Kamath, D.Y., Sigamani, A., Xavier, D. (2015). Prevention of Cardiovascular Disease: The Polypill Concept. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_29
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