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Non‐adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT
Author(s) -
Böhm Michael,
Lloyd Suzanne M.,
Ford Ian,
Borer Jeffrey S.,
Ewen Sebastian,
Laufs Ulrich,
Mahfoud Felix,
LopezSendon Jose,
Ponikowski Piotr,
Tavazzi Luigi,
Swedberg Karl,
Komajda Michel
Publication year - 2016
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.493
Subject(s) - ivabradine , medicine , heart failure , hazard ratio , placebo , clinical endpoint , cardiology , confidence interval , randomized controlled trial , proportional hazards model , heart rate , blood pressure , alternative medicine , pathology
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 I f ‐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.