Fixed Dose Combination Drug (Polypill)for Secondary Cardiovascular Prevention.

Summary

The aim of the FOCUS project is to test the Fixed Dose Combination concept for cardiovascular prevention in populations of different socio-economic characteristics. At the same time, FOCUS aims to understand the factors determining inappropriate prescribing for secondary cardiovascular prevention and those for poor patients adherence to treatment. This will allow FOCUS to establish recommendations for a better use of medication in patients with ischemic heart disease. In addition, after a successful completion of FOCUS, secondary prevention medication will be available and affordable for a large number of patients in both developed as well as developing countries. There are two Phases in this study: Phase 1: Is a descriptive, non interventional study. Phase 2: Is an interventional, randomized trial with prospective economic evaluation.

Timeline

Start

2012-01

Primary completion

2014-05

Completion

2014-06

Publications

• Background World Health Organization. Price, availability and affordability. An international comparison of chronic disease medicines. Background report prepared for the WHO Plannig Meeting on the Global Initiative for Treatment of Chronic Diseases, Cairo, December 2005
• Background European Cardiovascular Disease Statistics. British Heart Foundation and European Heart Network. 2005
• Background European Health Heart Charter. Available at www.heartcharter.eu
• Background Beaglehole R, Reddy S, Leeder SR. Poverty and human development: the global implications of cardiovascular disease. Circulation. 2007 Oct 23;116(17):1871-3. doi: 10.1161/CIRCULATIONAHA.107.736926. No abstract available.
• Background kaplan W. LR. Priority medicines for Europe and the World; 2004 November.
• Background Reddy KS. Cardiovascular diseases in the developing countries: dimensions, determinants, dynamics and directions for public health action. Public Health Nutr. 2002 Feb;5(1A):231-7. doi: 10.1079/phn2001298.
• Background Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet. 2003 Sep 13;362(9387):847-52. doi: 10.1016/S0140-6736(03)14338-3.
• Background Mackenbach JP, Stirbu I, Roskam AJ, Schaap MM, Menvielle G, Leinsalu M, Kunst AE; European Union Working Group on Socioeconomic Inequalities in Health. Socioeconomic inequalities in health in 22 European countries. N Engl J Med. 2008 Jun 5;358(23):2468-81. doi: 10.1056/NEJMsa0707519.
• Background Asaria P, Chisholm D, Mathers C, Ezzati M, Beaglehole R. Chronic disease prevention: health effects and financial costs of strategies to reduce salt intake and control tobacco use. Lancet. 2007 Dec 15;370(9604):2044-53. doi: 10.1016/S0140-6736(07)61698-5. Epub 2007 Dec 11.
• Background Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. doi: 10.1016/S0140-6736(04)17018-9.
• Background Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006 May 27;367(9524):1747-57. doi: 10.1016/S0140-6736(06)68770-9.
• Background Sanz GA. [Risk stratification in acute coronary syndromes: an unresolved issue]. Rev Esp Cardiol. 2007 Oct;60 Suppl 3:23-30. Spanish.
• Background Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003 Oct 27;163(19):2345-53. doi: 10.1001/archinte.163.19.2345.
• Background Chiuve SE, McCullough ML, Sacks FM, Rimm EB. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation. 2006 Jul 11;114(2):160-7. doi: 10.1161/CIRCULATIONAHA.106.621417. Epub 2006 Jul 3.
• Background Davies AR, Smeeth L, Grundy EM. Contribution of changes in incidence and mortality to trends in the prevalence of coronary heart disease in the UK: 1996 2005. Eur Heart J. 2007 Sep;28(17):2142-7. doi: 10.1093/eurheartj/ehm272. Epub 2007 Jul 18.
• Background Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71.
• Background Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; 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 Oct 8;366(9493):1267-78. doi: 10.1016/S0140-6736(05)67394-1. Epub 2005 Sep 27.
• Background Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA; AHA/ACC; National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006 May 16;113(19):2363-72. doi: 10.1161/CIRCULATIONAHA.106.174516. No abstract available.
• Background Fletcher GF, Bufalino V, Costa F, Goldstein LB, Jones D, Smaha L, Smith SC Jr, Stone N. Efficacy of drug therapy in the secondary prevention of cardiovascular disease and stroke. Am J Cardiol. 2007 Mar 27;99(6C):1E-35E. doi: 10.1016/j.amjcard.2007.02.001. Epub 2007 Mar 5. No abstract available.
• Background Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet. 2006 Aug 12;368(9535):581-8. doi: 10.1016/S0140-6736(06)69201-5.
• Background Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steg PG. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Arch Intern Med. 2006 Apr 10;166(7):787-96. doi: 10.1001/archinte.166.7.787.
• Background Doval HCT, C.D. Prevención secundaria de las enfermedades cardiovasculares. In: Evidencias en Cardiología. Buenos Aires: GEDIC; 2008.
• Background 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 Jun 28;326(7404):1423. doi: 10.1136/bmj.326.7404.1423.
• Background Mendis S, Abegunde D, Yusuf S, Ebrahim S, Shaper G, Ghannem H, Shengelia B. WHO study on Prevention of REcurrences of Myocardial Infarction and StrokE (WHO-PREMISE). Bull World Health Organ. 2005 Nov;83(11):820-9. Epub 2005 Nov 10.
• Background Antithrombotic Trialists' (ATT) Collaboration; 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. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S0140-6736(09)60503-1.
• Background EUROASPIRE I and II Group; European Action on Secondary Prevention by Intervention to Reduce Events. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and II in nine countries. EUROASPIRE I and II Group. European Action on Secondary Prevention by Intervention to Reduce Events. Lancet. 2001 Mar 31;357(9261):995-1001. doi: 10.1016/s0140-6736(00)04235-5.
• Background Heras M, Marrugat J, Aros F, Bosch X, Enero J, Suarez MA, Pabon P, Ancillo P, Loma-Osorio A, Rodriguez JJ, Subirana I, Vila J; en representacion de los investigadores del estudio PRIAMHO. [Reduction in acute myocardial infarction mortality over a five-year period]. Rev Esp Cardiol. 2006 Mar;59(3):200-8. Spanish.
• Background Kotseva K. Global preventive policies. Strategies at European and worldwide level. Rev Esp Cardiol. 2008 Sep;61(9):960-70. English, Spanish.
• Background Kristensen SD, Baumgartner H, Drexler H, Eeckhout E, Filippatos G, Gitt AK, Linde C, Pierard LA, Poldermans D, Schunkert H, Sipido KR, van der Wall EE, Fox K, Bax JJ; European Society of Cardiology. Highlights of the 2007 scientific sessions of the European Society of Cardiology Vienna, Austria, September 1-5, 2007. J Am Coll Cardiol. 2007 Dec 18;50(25):2421-30. doi: 10.1016/j.jacc.2007.10.010. No abstract available.
• Background Mendis S, Fukino K, Cameron A, Laing R, Filipe A Jr, Khatib O, Leowski J, Ewen M. The availability and affordability of selected essential medicines for chronic diseases in six low- and middle-income countries. Bull World Health Organ. 2007 Apr;85(4):279-88. doi: 10.2471/blt.06.033647.
• Background Trust WW. Second World Health Organization & Wellcome Trust Workshop. In: Secondary Prevention of Cardiovascular Disease in Low & Middle Income Countries - Building the Evidence Base on Secondary Prevention of CVD. 2007 6-8 June; London; 2007
• Background Kotseva K, Wood D, De Backer G, De Bacquer D, Pyorala K, Keil U; EUROASPIRE Study Group. Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries. Lancet. 2009 Mar 14;373(9667):929-40. doi: 10.1016/S0140-6736(09)60330-5.
• Background Gaziano TA, Galea G, Reddy KS. Scaling up interventions for chronic disease prevention: the evidence. Lancet. 2007 Dec 8;370(9603):1939-46. doi: 10.1016/S0140-6736(07)61697-3.
• Background Gaziano TA. Economic burden and the cost-effectiveness of treatment of cardiovascular diseases in Africa. Heart. 2008 Feb;94(2):140-4. doi: 10.1136/hrt.2007.128785.
• Background Beaglehole R, Ebrahim S, Reddy S, Voute J, Leeder S; Chronic Disease Action Group. Prevention of chronic diseases: a call to action. Lancet. 2007 Dec 22;370(9605):2152-7. doi: 10.1016/S0140-6736(07)61700-0. Epub 2007 Dec 11.
• Background Pharma 2020: the vision. Which path will you take? (Accessed at http://www.pwc.com/pharma.)
• Background Bosworth HB. Medication treatment adherence. Chapter 6, 147-94. In: Bosworth H, Oddone, E., Weinberger, M., ed. In:
• Background DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004 Mar;42(3):200-9. doi: 10.1097/01.mlr.0000114908.90348.f9.
• Background Gehi A, Haas D, Pipkin S, Whooley MA. Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study. Arch Intern Med. 2005 Nov 28;165(21):2508-13. doi: 10.1001/archinte.165.21.2508.
• Background DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000 Jul 24;160(14):2101-7. doi: 10.1001/archinte.160.14.2101.
• Background DiMatteo MR. Social support and patient adherence to medical treatment: a meta-analysis. Health Psychol. 2004 Mar;23(2):207-18. doi: 10.1037/0278-6133.23.2.207.
• Background Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007 Jan 10;297(2):177-86. doi: 10.1001/jama.297.2.177.
• Background Mukherjee D, Fang J, Chetcuti S, Moscucci M, Kline-Rogers E, Eagle KA. Impact of combination evidence-based medical therapy on mortality in patients with acute coronary syndromes. Circulation. 2004 Feb 17;109(6):745-9. doi: 10.1161/01.CIR.0000112577.69066.CB.
• Background Ho PM, Spertus JA, Masoudi FA, Reid KJ, Peterson ED, Magid DJ, Krumholz HM, Rumsfeld JS. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med. 2006 Sep 25;166(17):1842-7. doi: 10.1001/archinte.166.17.1842.
• Background Danchin N, Cambou JP, Hanania G, Kadri Z, Genes N, Lablanche JM, Blanchard D, Vaur L, Clerson P, Gueret P; USIC 2000 investigators. Impact of combined secondary prevention therapy after myocardial infarction: data from a nationwide French registry. Am Heart J. 2005 Dec;150(6):1147-53. doi: 10.1016/j.ahj.2005.01.058.
• Background Jackevicius CA, Li P, Tu JV. Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation. 2008 Feb 26;117(8):1028-36. doi: 10.1161/CIRCULATIONAHA.107.706820.
• Background World Bank Report: Public Policy and the Challenge of Chronic Noncommunicable Diseases. 2007. (Accessed at http://siteresources.worldbank.org/INTPH/Resources/PublicPolicyandNCDsWorldBank2007FullReport.pdf.)
• Background Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. doi: 10.1136/bmj.326.7404.1419.
• Background Wise J. Polypill holds promise for people with chronic disease. Bull World Health Organ. 2005 Dec;83(12):885-7. Epub 2006 Jan 30. No abstract available.
• Background Sleight P, Pouleur H, Zannad F. Benefits, challenges, and registerability of the polypill. Eur Heart J. 2006 Jul;27(14):1651-6. doi: 10.1093/eurheartj/ehi841. Epub 2006 Apr 7.
• Background Reddy KS. Is a multidrug regimen cost-effective for the prevention of cardiovascular disease in resource-poor countries? Nat Clin Pract Cardiovasc Med. 2007 Mar;4(3):130-2. doi: 10.1038/ncpcardio0799. Epub 2007 Jan 30. No abstract available.
• Background Reddy KS. The preventive polypill--much promise, insufficient evidence. N Engl J Med. 2007 Jan 18;356(3):212. doi: 10.1056/NEJMp068219. No abstract available.
• Background Herrick TM, Million RP. Tapping the potential of fixed-dose combinations. Nat Rev Drug Discov. 2007 Jul;6(7):513-4. doi: 10.1038/nrd2334. No abstract available.
• Background Fuster V, Sanz G. A polypill for secondary prevention: time to move from intellectual debate to action. Nat Clin Pract Cardiovasc Med. 2007 Apr;4(4):173. doi: 10.1038/ncpcardio0858. No abstract available.
• Background Combination Pharmacotherapy and Public Health Research Working Group. Combination pharmacotherapy for cardiovascular disease. Ann Intern Med. 2005 Oct 18;143(8):593-9. doi: 10.7326/0003-4819-143-8-200510180-00010.
• Background Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007 Aug;120(8):713-9. doi: 10.1016/j.amjmed.2006.08.033.
• Background Dickson M, Plauschinat CA. Compliance with antihypertensive therapy in the elderly: a comparison of fixed-dose combination amlodipine/benazepril versus component-based free-combination therapy. Am J Cardiovasc Drugs. 2008;8(1):45-50. doi: 10.2165/00129784-200808010-00006.
• Background Pan F, Chernew ME, Fendrick AM. Impact of fixed-dose combination drugs on adherence to prescription medications. J Gen Intern Med. 2008 May;23(5):611-4. doi: 10.1007/s11606-008-0544-x. Epub 2008 Feb 21.
• Background Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
• Background Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Applied Psychology Measurements 1977;1.
• Background Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, Czajkowski SM, DeBusk R, Hosking J, Jaffe A, Kaufmann PG, Mitchell P, Norman J, Powell LH, Raczynski JM, Schneiderman N; Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD). Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003 Jun 18;289(23):3106-16. doi: 10.1001/jama.289.23.3106.
• Castellano JM, Sanz G, Penalvo JL, Bansilal S, Fernandez-Ortiz A, Alvarez L, Guzman L, Linares JC, Garcia F, D'Aniello F, Arnaiz JA, Varea S, Martinez F, Lorenzatti A, Imaz I, Sanchez-Gomez LM, Roncaglioni MC, Baviera M, Smith SC Jr, Taubert K, Pocock S, Brotons C, Farkouh ME, Fuster V. A polypill strategy to improve adherence: results from the FOCUS project. J Am Coll Cardiol. 2014 Nov 18-25;64(20):2071-82. doi: 10.1016/j.jacc.2014.08.021. Epub 2014 Sep 1.
• Sanz G, Fuster V, Guzman L, Guglietta A, Arnaiz JA, Martinez F, Sarria A, Roncaglioni MC, Taubert K. The fixed-dose combination drug for secondary cardiovascular prevention project: improving equitable access and adherence to secondary cardiovascular prevention with a fixed-dose combination drug. Study design and objectives. Am Heart J. 2011 Nov;162(5):811-817.e1. doi: 10.1016/j.ahj.2011.08.012.

Drugs

Indications