Author + information
- Received July 18, 2014
- Revision received August 22, 2014
- Accepted August 22, 2014
- Published online November 18, 2014.
- José M. Castellano, MD, PhD∗,†,
- Ginés Sanz, MD, PhD∗,
- José L. Peñalvo, PhD∗,
- Sameer Bansilal, MD, MS†,
- Antonio Fernández-Ortiz, MD, PhD∗,‡,
- Luz Alvarez, BSc∗,
- Luis Guzmán, MD§,
- Juan Carlos Linares, MD§,
- Fernando García, MD, PhD‖,
- Fabiana D’Aniello, PhD‖,
- Joan Albert Arnáiz, MD, PhD¶,
- Sara Varea, BSc¶,
- Felipe Martínez, MD#,
- Alberto Lorenzatti, MD#,
- Iñaki Imaz, MD, PhD∗∗,
- Luis M. Sánchez-Gómez, MD, MSc∗∗,
- Maria Carla Roncaglioni, Biol Sci Dr††,
- Marta Baviera, PharmD††,
- Sidney C. Smith Jr., MD‡‡,
- Kathryn Taubert, PhD‡‡,
- Stuart Pocock, PhD∗,§§,
- Carlos Brotons, MD, PhD‖‖,
- Michael E. Farkouh, MD, MSc¶¶ and
- Valentin Fuster, MD, PhD∗,†∗ ()
- ∗Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
- †Icahn School of Medicine at Mount Sinai, New York, New York
- ‡Hospital Clínico San Carlos, Madrid, Spain
- §Federación Argentina de Cardiología, Córdoba, Argentina
- ‖FERRER Internacional, Barcelona, Spain
- ¶Fundació Clinic per la Recerca Biomèdica, Barcelona (FCRB), Spain
- #Instituto DAMIC, Cordoba, Argentina
- ∗∗Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- ††Istituto di Ricerche Farmacologiche “Mario Negri” (IRFMN) Milan, Italy
- ‡‡World Heart Federation (WHF), Geneva, Switzerland
- §§London School of Hygiene and Tropical Medicine, London, United Kingdom
- ‖‖Equip d'Atenció Primària Sardenya-Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
- ¶¶Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
- ↵∗Reprint requests and correspondence:
Dr. Valentin Fuster, The Mount Sinai Medical Center, One Gustave Levy Place, Box 1030, New York, New York 10029-6574.
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.
Objectives 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)
The study was funded by the 7th Framework Programme European Commission Consortium: Centro Nacional de Investigaciones Cardiovasculares CNIC (Madrid, Spain); Instituto Damic (Córdoba, Argentina), Istituto di Ricerche Farmacologiche “Mario Negri” (IRFMN, Milan, Italy), Fundació Clinic per la Recerca Biomèdica (Barcelona, Spain), World Heart Federation (Geneva, Switzerland), Federación Argentina de Cardiología (Buenos Aires, Argentina), FERRER Internacional (Barcelona, Spain), Instituto de Salud Carlos III (Madrid, Spain), and ARTTIC (Paris, France). Drs. D’Aniello and Garcia are employees of Grupo Ferrer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. P. K. Shah, MD, and Paul Armstrong, MD, served as the Guest Editors for this article.
- Received July 18, 2014.
- Revision received August 22, 2014.
- Accepted August 22, 2014.
- American College of Cardiology Foundation