Michael Böhm1, Suzanne M Lloyd2, Ian Ford2, Jeffrey S Borer3, Sebastian Ewen1, Ulrich Laufs1, Felix Mahfoud1, Jose Lopez-Sendon4, Piotr Ponikowski5, Luigi Tavazzi6, Karl Swedberg7,8, Michel Komajda9. 1. Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany. 2. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. 3. 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. 4. Hospital Universitario La PAZ, Cardiology Department, Instituto de Investigation, Madrid, Spain. 5. Department of Cardiology, Military Hospital, Wrocław, Poland. 6. Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy. 7. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. 8. National Heart and Lung Institute, Imperial College, London, UK. 9. Istitute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie Paris VI University, La Pitié-Salpétrière Hospital, Paris, France.
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ISRCTN70429960.
RCT Entities:
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ISRCTN70429960.
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