title: Heart Rate reduction by IVabradine for improvement of ENDothELial function in patients with coronary artery disease: the RIVENDEL study.
abstract: OBJECTIVE
  Data from experimental studies suggest that thefcurrent-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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy. f.mangiacapra@unicampus.it.
authors: Fabio
authors: http://orcid.org/0000-0002-3505-0716
authors: F
authors: Mangiacapra
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Iginio
authors: I
authors: Colaiori
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Elisabetta
authors: E
authors: Ricottini
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Francesco
authors: F
authors: Balducci
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Antonio
authors: A
authors: Creta
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Chiara
authors: C
authors: Demartini
authors: Unit of Drug Science, Department of Medicine, Campus Bio-Medico University, Rome, Italy.
authors: Giorgio
authors: G
authors: Minotti
authors: Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Via Álvaro del Portillo, 200, 00128, Rome, Italy.
authors: Germano
authors: G
authors: Di Sciascio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012384:Rome; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: Coronary artery disease; Endothelial function; Percutaneous coronary intervention; Pharmacology