We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov Menu

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

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: March 23, 2011
Last Update Posted: July 15, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Mario Negri Institute for Pharmacological Research
Rusculleda Foundation Instituto DAMIC
Fundacion Clinic per a la Recerca Biomédica
ARTTIC International Management Services
Federación Argentina de Cardiología FAC
World Health Organization
Instituto de Salud Carlos III
Ferrer Internacional S.A.
Information provided by (Responsible Party):
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

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.

Condition Intervention Phase
Myocardial Infarction Drug: FDC Drug: Separately drugs, simvastatin, aspirin and ramipril Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Improving Equitable Acces and Adherence to Secondary Prevention Therapy With a Fixed-Dose Combination Drug

Resource links provided by NLM:

Further study details as provided by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III:

Primary Outcome Measures:
  • Proportion of patients receiving AAS, an ACE inhibitor and a statin among those without contraindications to any of these drugs Adherence to treatment measured by: Morinsky-Green test and Pill accountability. [ Time Frame: 18 months ]
    Phase 1

  • Adherence to treatment measured by the Morisky-Green questionnaire [ Time Frame: 18 months ]

    Phase 1:

    Adherence to treatment measured by the Morisky-Green questionnaire. According to this, patients will be classified as "Good adherents" when the total score ranges between 16 and 20 and as "Poor adherents" if the total score is <16 points

  • Treatment adherence measured by: Morisky-Green test: (Good adherence score 16-20) at 1 and 9 months. [ Time Frame: 18 months ]
    Phase 2

  • Treatment adherence measured by: Pill counts at 1-4-9 months. (Good adherence 80-110% PC) [ Time Frame: 18 months ]
    Phase 2

Secondary Outcome Measures:
  • Blood Pressure and Lipid Profile (LDL-cholesterol) at 1 and 9 months [ Time Frame: 18 months ]
    Phase 2

  • Safety and tolerability: Adverse events and rate of treatment withdrawal. [ Time Frame: 18 months ]
    Phase 2

Enrollment: 2118
Study Start Date: January 2012
Study Completion Date: June 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FDC Fixed Dose Combination Drug: FDC
FDC includes a combination of 100 mg aspirin, 40 mg simvastatin, and 2.5;5;10 mg Ramipril
Active Comparator: Conventional treatment Drug: Separately drugs, simvastatin, aspirin and ramipril
Aspirin 100 mg once a day Ramipril 2.5; 5; 10 mg once a day Simvastatin 40 mg once a day

Detailed Description:

The specific objective of the FOCUS project is to prove that:

  1. Better knowledge of factors relates to inappropriate use of secondary cardiovascular prevention drugs and lack of adherence to treatment will help to design new strategies for improving patients' management.
  2. A Fixed Dose Combination (FDC, polypill) including three components with a well demonstrated efficacy will improve secondary prevention in coronary patients by decreasing inappropriate prescribing and by reducing complexity of treatment and lack of adherence.

    • Phase 1 is a descriptive, non-interventional study. Its aim is to provide a comprehensive analysis of potential factors precluding adequate secondary prevention, including Health system characteristics, drugs affordability and availability, as well as patients' characteristics. Differences between the two studied regions (Europe and South America) will be analyzed.
    • Phase 2 is an interventional, randomized trial with prospective economic evaluation. It will be organised as a two-arm, randomised, parallel, multinational study. Patients completing the Phase 1, and fulfilling inclusion/exclusion criteria (see below), will be included in Phase 2. Patients will be randomized to receive a FDC of ramipril, simvastatin and acetylsalicylic acid or the three medications separately.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Phase 1: All patients, male and female, 40 years of age or older, with a history of ST-elevation AMI within the last 2 years, attending any of the selected sites and signing the consent
  • Phase 2: All patients, male and female, 40 years of age or older, with a history of ST-elevation AMI within the last 2 years, attending any of the selected sites and signing the consent Patients in whom secondary prevention with ASA, statin and ACEI is indicated, Signing informed consent

Exclusion Criteria:

  • Phase 1: Patients in which any of the components of the FDC is contraindicated. Living in a nursing home. Memtal illness limiting the capacity of
  • Phase 2:Secondary dyslipemia, Patients in which any of the components of the FDC is contraindicated, Living in a nursing home, Mental illness limiting the capacity of self care, Participating in another trial, , Previous Percutaneous Transluminal Coronary Angioplasty (PTCA) with a drug eluting stent (DES) whitin the last year, Severe Congestive Heart Failure (NYHA III-IV), Serum creatinine >2 mg/dl, any condition limiting life expectancy <2 years. Pregnant or premenopausal women.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01321255

  Show 69 Study Locations
Sponsors and Collaborators
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Mario Negri Institute for Pharmacological Research
Rusculleda Foundation Instituto DAMIC
Fundacion Clinic per a la Recerca Biomédica
ARTTIC International Management Services
Federación Argentina de Cardiología FAC
World Health Organization
Instituto de Salud Carlos III
Ferrer Internacional S.A.
Principal Investigator: Valentín Fuster, MD PhD Centro Nacional de Investigaciones Cardiovasculares Carlos III
Study Director: Ginés Sanz, MD PhD Centro Nacional de Investigaciones Cardiovasculares Carlos III
  More Information

Additional Information:
CNIC  This link exits the ClinicalTrials.gov site

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
European Cardiovascular Disease Statistics. British Heart Foundation and European Heart Network. 2005
European Health Heart Charter. Available at www.heartcharter.eu
Beaglehole R, Reddy S, Leeder SR. Poverty and human development: the global implications of cardiovascular disease. Circulation. 2007 Oct 23;116(17):1871-3. Review.
kaplan W. LR. Priority medicines for Europe and the World; 2004 November.
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. Review.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet. 2003 Sep 13;362(9387):847-52.
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. Erratum in: N Engl J Med. 2008 Sep 18;359(12):e14.
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. Epub 2007 Dec 11. Review. Erratum in: Lancet. 2007 Dec 15;370(9604):2004.
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.
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.
Sanz GA. [Risk stratification in acute coronary syndromes: an unresolved issue]. Rev Esp Cardiol. 2007 Oct;60 Suppl 3:23-30. Spanish.
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.
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. Epub 2006 Jul 3.
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. Epub 2007 Jul 18.
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. Erratum in: BMJ 2002 Jan 19;324(7330):141.
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. Epub 2005 Sep 27. Erratum in: Lancet. 2005 Oct 15-21;366(9494):1358. Lancet. 2008 Jun 21;371(9630):2084.
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. Erratum in: Circulation. 2006 Jun 6;113(22):e847.
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. Epub 2007 Mar 5. Review.
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. Review.
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.
Doval HCT, C.D. Prevención secundaria de las enfermedades cardiovasculares. In: Evidencias en Cardiología. Buenos Aires: GEDIC; 2008.
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. Review.
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.
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.
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.
Heras M, Marrugat J, Arós F, Bosch X, Enero J, Suárez MA, Pabón P, Ancillo P, Loma-Osorio A, Rodríguez JJ, Subirana I, Vila J; en representación 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.
Kotseva K. Global preventive policies. Strategies at European and worldwide level. Rev Esp Cardiol. 2008 Sep;61(9):960-70. English, Spanish.
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.
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.
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
Kotseva K, Wood D, De Backer G, De Bacquer D, Pyörälä 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.
Gaziano TA, Galea G, Reddy KS. Scaling up interventions for chronic disease prevention: the evidence. Lancet. 2007 Dec 8;370(9603):1939-46. Review.
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. Review.
Beaglehole R, Ebrahim S, Reddy S, Voûte J, Leeder S; Chronic Disease Action Group. Prevention of chronic diseases: a call to action. Lancet. 2007 Dec 22;370(9605):2152-7. Epub 2007 Dec 11. Review.
Pharma 2020: the vision. Which path will you take? (Accessed at http://www.pwc.com/pharma.)
Bosworth HB. Medication treatment adherence. Chapter 6, 147-94. In: Bosworth H, Oddone, E., Weinberger, M., ed. In:
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.
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.
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.
DiMatteo MR. Social support and patient adherence to medical treatment: a meta-analysis. Health Psychol. 2004 Mar;23(2):207-18.
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.
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.
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.
Danchin N, Cambou JP, Hanania G, Kadri Z, Genès N, Lablanche JM, Blanchard D, Vaur L, Clerson P, Guéret 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.
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.
World Bank Report: Public Policy and the Challenge of Chronic Noncommunicable Diseases. 2007. (Accessed at http://siteresources.worldbank.org/INTPH/Resources/PublicPolicyandNCDsWorldBank2007FullReport.pdf.)
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. Erratum in: BMJ. 2006 Sep;60(9):823. BMJ. 2003 Sep 13;327(7415):586.
Wise J. Polypill holds promise for people with chronic disease. Bull World Health Organ. 2005 Dec;83(12):885-7. Epub 2006 Jan 30.
Sleight P, Pouleur H, Zannad F. Benefits, challenges, and registerability of the polypill. Eur Heart J. 2006 Jul;27(14):1651-6. Epub 2006 Apr 7. Review.
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. Epub 2007 Jan 30.
Reddy KS. The preventive polypill--much promise, insufficient evidence. N Engl J Med. 2007 Jan 18;356(3):212.
Herrick TM, Million RP. Tapping the potential of fixed-dose combinations. Nat Rev Drug Discov. 2007 Jul;6(7):513-4.
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.
Combination Pharmacotherapy and Public Health Research Working Group. Combination pharmacotherapy for cardiovascular disease. Ann Intern Med. 2005 Oct 18;143(8):593-9. Review. Erratum in: Ann Intern Med. 2006 Jul 4;145(1):79.
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.
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.
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.
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.
Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Applied Psychology Measurements 1977;1.
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
ClinicalTrials.gov Identifier: NCT01321255     History of Changes
Other Study ID Numbers: FOCUS
2010-022492-54 ( EudraCT Number )
Health-F2-2009-241559 ( Other Grant/Funding Number: Frame of Seventh Investigation Marco Programme, Technological development and Innovation of the EU )
First Submitted: March 21, 2011
First Posted: March 23, 2011
Last Update Posted: July 15, 2014
Last Verified: July 2014

Keywords provided by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III:
Myocardial Infarction
Treatment Adherence

Additional relevant MeSH terms:
Myocardial Infarction
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents

To Top