title: Efficacy and safety of ivabradine in patients with severe chronic systolic heart failure (from the SHIFT study).
abstract: A post hoc analysis of Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) explored the efficacy and safety of ivabradine in severe heart failure (HF) as denoted by left ventricular ejection fraction (LVEF) ≤20% and/or New York Heart Association (NYHA) class IV. The SHIFT population (LVEF ≤35%, heart rate ≥70 beats/min, and sinus rhythm) comprised 712 patients with severe (defined previously) and 5,973 with less severe (NYHA classes II or III and LVEF >20%) HF, all randomized to ivabradine or placebo on a background of guideline-defined standard care. The rate of primary composite end point of cardiovascular death or HF hospitalization with placebo was higher in severe (42%) than less severe (27%) HF (p <0.001). Treatment with ivabradine in severe HF was associated with relative risk reductions indistinguishable from those of less severe disease for the primary end point (16% reduction), all-cause death (22%), cardiovascular death (22%), HF death (37%), and HF hospitalization (17%; all p values for interaction: NS). NYHA class improved in 38% (n = 129) ivabradine-treated patients with severe HF versus 29% (n = 104) placebo-treated patients (p = 0.009). In the 272 patients with severe HF and baseline heart rate ≥75 beats/min (the indication approved by the European Medicines Agency), ivabradine reduced the primary end point by 25% (p = 0.045), HF hospitalization by 30% (p = 0.042), and cardiovascular death by 32% (p = 0.034). Ivabradine's safety profile in severe HF was indistinguishable from less severe. In conclusion, our analysis confirms that heart rate reduction with ivabradine can be safely used in severe HF and may improve clinical outcomes independently of disease severity.
authors: Division of Cardiovascular Medicine, The Howard Gilman Institute for Heart Valve Disease and the Schiavone Institute for Cardiovascular Translational Research, State University of New York Downstate Medical Center, New York, New York. Electronic address: canadad45@aol.com.
authors: Jeffrey S
authors: JS
authors: Borer
authors: Klinik für Innere Medizin III, Universitätskliniken des Saarlandes, Homburg, Saar, Germany.
authors: Michael
authors: M
authors: Böhm
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
authors: Ian
authors: I
authors: Ford
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
authors: Michele
authors: M
authors: Robertson
authors: Department of Cardiology, Pierre et Marie Curie Paris VI University, La Pitié-Salpétrière Hospital, Paris, France.
authors: Michel
authors: M
authors: Komajda
authors: Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy.
authors: Luigi
authors: L
authors: Tavazzi
authors: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors: Karl
authors: K
authors: Swedberg
mesh_terms: D001552:Benzazepines / Q000008:administration & dosage*; D054815:Cyclic Nucleotide-Gated Cation Channels; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine