Doesch Andreas O, Celik Sultan, Ehlermann Philipp, Frankenstein Lutz, Zehelein Jörg, Koch Achim, Katus Hugo A, Dengler Thomas J
Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Transplantation. 2007 Oct 27;84(8):988-96. doi: 10.1097/01.tp.0000285265.86954.80.
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.
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.
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.
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.
心脏移植受者的移植心脏去神经支配会导致窦性心动过速，有时需要药物降低心率。心脏移植后，尚未将If通道拮抗剂伊伐布雷定与β受体阻滞剂进行比较。在心脏移植受者中，将一种已确立的降低心率药物（琥珀酸美托洛尔）与一种新型药物（伊伐布雷定）连续进行比较，研究心率控制、耐受性、短期安全性以及对运动能力的影响。
对25例心脏移植受者，在未用药（基线）时以及在接受美托洛尔和伊伐布雷定连续8周治疗后，评估心率、运动能力和患者偏好。
5例患者因副作用停药（美托洛尔：4例，伊伐布雷定：1例）；对完成两个连续治疗期的20例患者进行了符合方案分析。使用β受体阻滞剂时，平均心率从基线（96.5±7.0次/分钟）降至84.4±8.8次/分钟（与基线相比，P = 0.0004），使用伊伐布雷定时降至76.2±8.9次/分钟（与基线相比，P = 0.0001；与β受体阻滞剂相比，P = 0.003）。两种药物均未改变通过运动心肺功能测试测得的运动能力。使用伊伐布雷定时未观察到与免疫抑制剂的相关药代动力学相互作用；安全实验室值未改变。使用β受体阻滞剂治疗期间，45%的患者出现轻度不良反应，使用伊伐布雷定治疗期间为20%。问卷调查分析表明患者更倾向于使用伊伐布雷定降低心率。
在心脏移植受者中，伊伐布雷定降低心率有效，且耐受性可能优于β受体阻滞剂治疗。尽管心脏移植后心率的预后作用尚不清楚，但伊伐布雷定可能带来相关的症状改善，尤其是在β受体阻滞剂不耐受的情况下。
