title: Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial.
abstract: OBJECTIVE
  To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status.
  
  
  RESULTS
  This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07-1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13-1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23-1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68-0.94 and HR 0.84, 95% CI, 0.75-0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo.
  
  
  CONCLUSIONS
  Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.
authors.affiliation: Institute of Cardio-Metabolism and Nutrition (ICAN), Department of Cardiology, Pierre et Marie Curie University, Paris VI and Pitié-Salpêtrière Hospital, AP-HP, 47-83 Boulevard de l'Hôpital, 75013, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
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: Robertson Centre for Biostatistics, University of Glasgow, UK.
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Francq
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
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: Robertson Centre for Biostatistics, University of Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden, and National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
mesh_terms: D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D048909:Diabetes Complications; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: Diabetes mellitus; Insulin; Ischaemic heart failure; Ivabradine; Severe heart failure