Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine.
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.
Doesch
Andreas O
AO
Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Andreas.Doesch@med.uni-heidelberg.de
Celik
Sultan
S
Ehlermann
Philipp
P
Frankenstein
Lutz
L
Zehelein
Jörg
J
Koch
Achim
A
Katus
Hugo A
HA
Dengler
Thomas J
TJ
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
D001552:Benzazepines; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine