Mangiacapra Fabio, Colaiori Iginio, Ricottini Elisabetta, Balducci Francesco, Creta Antonio, Demartini Chiara, Minotti Giorgio, Di Sciascio Germano
Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
Unit of Drug Science, Department of Medicine, Campus Bio-Medico University, Rome, Italy.
Clin Res Cardiol. 2017 Jan;106(1):69-75. doi: 10.1007/s00392-016-1024-7. Epub 2016 Aug 12.
Data from experimental studies suggest that the current-inhibitor ivabradine may reduce oxidative stress and improve endothelial function. We aimed to evaluate the effect of ivabradine on endothelial function in patients with coronary artery disease (CAD) after complete revascularization with percutaneous coronary angioplasty (PCI).
At least 30 days after PCI, 70 patients were randomized (T0) to receive ivabradine 5 mg twice daily (ivabradine group, n = 36) or to continue with standard medical therapy (control group, n = 34). After 4 weeks (T1), ivabradine dose was adjusted up to 7.5 mg twice daily in patients with heart rate (HR) at rest >60 bpm, and thereafter continued for additional 4 weeks (T2). At all timings, brachial artery reactivity was assessed by flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD). No significant differences were observed at T0 between ivabradine and control groups in terms of HR (68.0 ± 6.4 vs. 67.6 ± 6.4 bpm; p = 0.803), FMD (8.7 ± 4.9 vs. 8.0 ± 5.5 %; p = 0.577) and NMD (12.7 ± 6.7 vs. 13.3 ± 6.2 %; p = 0.715). Over the study period, a significant reduction of HR (65.2 ± 5.9 bpm at T1, 62.2 ± 5.7 bpm at T2; p < 0.001), and improvement of FMD (12.2 ± 6.2 % at T1, 15.0 ± 7.7 % at T2; p < 0.001) and NMD (16.6 ± 10.4 % at T1, 17.7 ± 10.8 at T2; p < 0.001) were observed in the ivabradine group, while no significant changes were observed in the control group. In the ivabradine group, a moderate negative correlation was observed between the HR variation and FMD variation from T1 to T3 (r = -0.448; p = 0.006).
In patients with CAD undergoing complete revascularization with PCI, addition of ivabradine to the standard medical therapy produces a significant improvement in endothelial function. This effect seems to be related to HR reduction. ClinicalTrials.gov number, NCT02681978.
实验研究数据表明，当前的抑制剂伊伐布雷定可能会降低氧化应激并改善内皮功能。我们旨在评估伊伐布雷定对经皮冠状动脉介入治疗（PCI）实现完全血运重建后的冠心病（CAD）患者内皮功能的影响。
PCI术后至少30天，70例患者被随机分组（T0），分别接受每日两次5mg伊伐布雷定治疗（伊伐布雷定组，n = 36）或继续接受标准药物治疗（对照组，n = 34）。4周后（T1），静息心率（HR）>60次/分的患者将伊伐布雷定剂量上调至每日两次7.5mg，此后继续治疗4周（T2）。在所有时间点，通过血流介导的血管舒张（FMD）和硝酸甘油介导的血管舒张（NMD）评估肱动脉反应性。在T0时，伊伐布雷定组和对照组在HR（68.0±6.4 vs. 67.6±6.4次/分；p = 0.803）、FMD（8.7±4.9 vs. 8.0±5.5%；p = 0.577）和NMD（12.7±6.7 vs. 13.3±6.2%；p = 0.715）方面未观察到显著差异。在研究期间，伊伐布雷定组的HR显著降低（T1时为65.2±5.9次/分，T2时为62.2±5.7次/分；p < 0.001），FMD（T1时为12.2±6.2%，T2时为15.0±7.7%；p < 0.001）和NMD（T1时为16.6±10.4%，T2时为17.7±10.8；p < 0.001）得到改善，而对照组未观察到显著变化。在伊伐布雷定组中，观察到从T1到T3的HR变化与FMD变化之间存在中度负相关（r = -0.448；p = 0.00）。
在接受PCI完全血运重建的CAD患者中，在标准药物治疗基础上加用伊伐布雷定可显著改善内皮功能。这种作用似乎与心率降低有关。ClinicalTrials.gov编号，NCT02681978。
