title: A polypill strategy to improve adherence: results from the FOCUS project.
abstract: BACKGROUND
  Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (MI) is low after the first 6 months. The use of fixed-dose combinations (FDC) has been shown to improve treatment adherence and risk factor control. However, no previous randomized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients.
  
  
  OBJECTIVE
  The cross-sectional FOCUS (Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention) study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI. Additionally, 695 patients from Phase 1 were randomized into a controlled trial (Phase 2) to test the effect of a polypill (containing aspirin 100 mg, simvastatin 40 mg, and ramipril 2.5, 5, or 10 mg) compared with the 3 drugs given separately on adherence, blood pressure, and low-density lipoprotein cholesterol, as well as safety and tolerability over a period of 9 months of follow-up.
  
  
  METHODS
  In Phase 1, a 5-country cohort of 2,118 patients was analyzed. Patients were randomized to either the polypill or 3 drugs separately for Phase 2. Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire (MAQ) and pill count (patients had to meet both criteria for adherence at the in-person visit to be considered adherent).
  
  
  RESULTS
  In Phase 1, overall CV medication adherence, defined as an MAQ score of 20, was 45.5%. In a multivariable regression model, the risk of being nonadherent (MAQ <20) was associated with younger age, depression, being on a complex medication regimen, poorer health insurance coverage, and a lower level of social support, with consistent findings across countries. In Phase 2, the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up: 50.8% versus 41% (p = 0.019; intention-to-treat population) and 65.7% versus 55.7% (p = 0.012; per protocol population) when using the primary endpoint, attending the final visit with MAQ = 20 and high pill count (80% to 110%) combined, to assess adherence. Adherence also was higher in the FDC group when measured by MAQ alone (68% vs. 59%, p = 0.049). No treatment difference was found at follow-up in mean systolic blood pressure (129.6 mm Hg vs. 128.6 mm Hg), mean low-density lipoprotein cholesterol levels (89.9 mg/dl vs. 91.7 mg/dl), serious adverse events (23 vs. 21), or death (1, 0.3% in each group).
  
  
  CONCLUSIONS
  For secondary prevention following acute MI, younger age, depression, and a complex drug treatment plan are associated with lower medication adherence. Meanwhile, adherence is increased in patients with higher insurance coverage levels and social support. Compared with the 3 drugs given separately, the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI. (Fixed Dose Combination Drug [Polypill] for Secondary Cardiovascular Prevention [FOCUS]; NCT01321255).
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: José M
authors.initials: JM
authors.lastname: Castellano
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Ginés
authors.initials: G
authors.lastname: Sanz
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Peñalvo
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Ortiz
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Luz
authors.initials: L
authors.lastname: Alvarez
authors.affiliation: Federación Argentina de Cardiología, Córdoba, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Guzmán
authors.affiliation: Federación Argentina de Cardiología, Córdoba, Argentina.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Linares
authors.affiliation: FERRER Internacional, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: García
authors.affiliation: FERRER Internacional, Barcelona, Spain.
authors.forename: Fabiana
authors.initials: F
authors.lastname: D'Aniello
authors.affiliation: Fundació Clinic per la Recerca Biomèdica, Barcelona (FCRB), Spain.
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Arnáiz
authors.affiliation: Fundació Clinic per la Recerca Biomèdica, Barcelona (FCRB), Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Varea
authors.affiliation: Instituto DAMIC, Cordoba, Argentina.
authors.forename: Felipe
authors.initials: F
authors.lastname: Martínez
authors.affiliation: Instituto DAMIC, Cordoba, Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lorenzatti
authors.affiliation: Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Imaz
authors.affiliation: Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Sánchez-Gómez
authors.affiliation: Istituto di Ricerche Farmacologiche "Mario Negri" (IRFMN) Milan, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Roncaglioni
authors.affiliation: Istituto di Ricerche Farmacologiche "Mario Negri" (IRFMN) Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Baviera
authors.affiliation: World Heart Federation (WHF), Geneva, Switzerland.
authors.forename: Sidney C
authors.initials: SC
authors.lastname: Smith
authors.affiliation: World Heart Federation (WHF), Geneva, Switzerland.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Taubert
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Equip d'Atenció Primària Sardenya-Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Brotons
authors.affiliation: Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.affiliation: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: valentin.fuster@mountsinai.org.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
mesh_terms: D000368:Aged; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology*; D011446:Prospective Studies; D055502:Secondary Prevention / Q000379:methods*
chemical_list: D002317:Cardiovascular Agents; D004338:Drug Combinations
keywords: adherence; polypill; secondary prevention