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: Andreas O Doesch, Sultan Celik, Philipp Ehlermann, Lutz Frankenstein, Jörg Zehelein, Achim Koch, Hugo A Katus, Thomas J Dengler
• Journal: Transplantation (Transplantation) Vol. 84 Issue 8 Pg. 988-96 (Oct 27 2007) ISSN: 0041-1337 [Print] United States
• PMID: 17989604 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Benzazepines
• Calcium Channel Blockers
• Cardiotonic Agents
• Cyclic Nucleotide-Gated Cation Channels
• Ivabradine

Topics

• Adult
• Aged
• Benzazepines (adverse effects, pharmacology, therapeutic use)
• Calcium Channel Blockers (adverse effects, pharmacology, therapeutic use)
• Cardiotonic Agents (adverse effects, pharmacology, therapeutic use)
• Cyclic Nucleotide-Gated Cation Channels (antagonists & inhibitors)
• Exercise Tolerance
• Female
• Heart Rate (drug effects)
• Heart Transplantation (adverse effects)
• Humans
• Ivabradine
• Male
• Middle Aged
• Tachycardia (drug therapy, etiology)