title: Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine.
abstract: BACKGROUND
  Graft denervation in heart transplant recipients causes sinus tachycardia, occasionally requiring pharmacologic heart rate reduction. The If channel antagonist ivabradine has not been compared to beta-blocker after heart transplantation. Heart rate control, tolerability, short-term safety, and effects on exercise capacity were studied consecutively with an established heart rate-reducing drug (metoprolol succinate) compared to a novel agent (ivabradine) in heart transplant recipients.
  
  
  METHODS
  In 25 heart transplant recipients, heart rate, exercise capacity, and patient preference were assessed under no medication (baseline) and after consecutive 8-week treatment periods under metoprolol and ivabradine.
  
  
  RESULTS
  Drug discontinuation following side effects occurred in 5 patients (metoprolol: 4, ivabradine: 1); per-protocol analysis was performed on 20 patients completing both consecutive treatment periods. Mean heart rate was reduced from baseline (96.5+/-7.0 bpm) to 84.4+/-8.8 bpm on beta-blocker (P=0.0004 vs. baseline) and to 76.2+/-8.9 bpm with ivabradine (P=0.0001 vs. baseline and P=0.003 vs. beta-blocker). Exercise capacity by spiroergometry was not altered by either drug. Relevant pharmacokinetic interaction with immunosuppressants was not seen under ivabradine; safety laboratory values were unchanged. Mild adverse effects were noted in 45% of patients during beta-blocker and 20% during ivabradine treatment. Questionnaire analysis demonstrated patient preference for heart rate reduction with ivabradine.
  
  
  CONCLUSIONS
  Heart rate reduction with ivabradine is effective and potentially better tolerated than beta-blocker therapy in heart transplant recipients. Although the prognostic role of heart rate after HTX is unknown, ivabradine may offer relevant symptomatic benefit, especially in cases of beta-blocker intolerance.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Andreas.Doesch@med.uni-heidelberg.de
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.forename: Sultan
authors.initials: S
authors.lastname: Celik
authors.forename: Philipp
authors.initials: P
authors.lastname: Ehlermann
authors.forename: Lutz
authors.initials: L
authors.lastname: Frankenstein
authors.forename: Jörg
authors.initials: J
authors.lastname: Zehelein
authors.forename: Achim
authors.initials: A
authors.lastname: Koch
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D017079:Exercise Tolerance; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D013610:Tachycardia / Q000188:drug therapy* / Q000209:etiology
chemical_list: D001552:Benzazepines; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine