title: Non-adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT.
abstract: In heart failure, non-adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non-adherence to outcomes, hospitalizations with non-adherence, and the influence of non-adherence on treatment effects of heart rate lowering with ivabradine.
  
  
  
  In the randomized, controlled Systolic Heart failure treatment with the If-inhibitor ivabradine Trial (SHIFT), we studied the effect of non-adherence (n = 1287) compared with adherence (n = 5204) on cardiovascular outcomes. After adjustment, non-adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91-4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non-adherent during the trial (P for interaction = 0.54). Patients with a previous hospitalization were more likely to become non-adherent thereafter.
  
  
  
  Non-adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non-adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non-adherent and represent a group of particularly high-risk patients in whom special attention to stimulate adherence may be valuable.
  
  
  
  ISRCTN70429960.
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Lloyd
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Division of Cardiovascular Medicine, The Howard Gilman Institute for Heart Valve Diseases and the Schiavone Institute for Cardiovascular Translational Research, SUNY Downstate Medical Center, Brooklyn and New York, NY, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ewen
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.affiliation: Hospital Universitario La PAZ, Cardiology Department, Instituto de Investigation, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.affiliation: Department of Cardiology, Military Hospital, Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.|National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Istitute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie Paris VI University, La Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010919:Placebos; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016903:Drug Monitoring
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D010919:Placebos; D000077550:Ivabradine
keywords: Adherence; Cardiovascular hospitalizations; Heart failure; Heart rate; SHIFT