title: Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in Patients with Stable Coronary Artery Disease: Beyond the Heart Rate.
abstract: BACKGROUND
  Coronary flow velocity reserve (CFVR) is an important prognostic marker in patients with stable coronary artery disease (CAD). Beta-blockers and ivabradine have been shown to improve CFVR in patients with stable CAD, but their effects were never compared. The aim of the current study was to compare the effects of bisoprolol and ivabradine on CFVR in patients with stable CAD.
  
  
  METHODS
  Patients in sinus rhythm with stable CAD were enrolled in this prospective, randomized, double-blind trial. Patients had to be in a stable condition for at least 15 days before enrollment, on their usual therapy. Patients who were receiving beta-blockers or ivabradine entered a 2-week washout period from these drugs before randomization. Transthoracic Doppler-derived CFVR was assessed in left anterior descending coronary artery, and was calculated as the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV). Hyperemic CFV was obtained using dipyridamole administration using standard protocols. After CFVR assessment, patients were randomized to ivabradine or bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month after the end of the up-titration phase.
  
  
  RESULTS
  Fifty-nine patients (38 male, 21 female; mean age 69 ± 9 years) were enrolled. Transthoracic Doppler-derived assessment of CFV and CFVR was successfully performed in all patients. Baseline characteristics were similar between the bisoprolol and ivabradine groups. No patient dropped out during the study. At baseline, rest and hyperemic peak CFV as well as CFVR was not significantly different in the ivabradine and bisoprolol groups. After the therapy, resting peak CFV significantly decreased in both the ivabradine and bisoprolol groups, but there was no significant difference between the groups (ivabradine group 20.7 ± 4.6 vs. 22.8 ± 5.2, P < 0.001; bisoprolol group 20.1 ± 4.1 vs. 22.1 ± 4.3, P < 0.001). However, hyperemic peak CFV significantly increased in both groups, but to a greater extent in patients treated with ivabradine (ivabradine: 70.7 ± 9.4 vs. 58.8 ± 9.2, P < 0.001; bisoprolol: 65 ± 8.3 vs. 58.7 ± 8.2, P < 0.001). Accordingly, CFVR significantly increased in both groups (ivabradine 3.52 ± 0.64 vs. 2.67 ± 0.55, P < 0.001; bisoprolol 3.35 ± 0.70 vs. 2.72 ± 0.55, P < 0.001), but it was significantly higher in ivabradine group, despite a similar decrease in heart rate (63 ± 7 vs. 61 ± 6; P not significant).
  
  
  CONCLUSIONS
  Ivabradine improves hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with stable CAD, despite a similar decrease in heart rate. These data demonstrate that the benefits from ivabradine therapy go beyond the heart rate. This could be due to a different mechanism such as diastolic perfusion time, isovolumic ventricular relaxation, end-diastolic pressure, and collaterals.
  
  
  BACKGROUND
  Servier.
authors: Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, SA, Italy. ercoletagliamonte@gmail.com.
authors: Ercole
authors: E
authors: Tagliamonte
authors: Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, SA, Italy.
authors: Teresa
authors: T
authors: Cirillo
authors: Department of Cardiology, Division of Cardiology, dell'Angelo Hospital, Mestre-Venice, Italy.
authors: Fausto
authors: F
authors: Rigo
authors: Cardiology Division, Santa Maria della Misericordia Hospital, Sorrento, Naples, Italy.
authors: Costantino
authors: C
authors: Astarita
authors: Cardiology Division, Santa Maria della Misericordia Hospital, Sorrento, Naples, Italy.
authors: Antonino
authors: A
authors: Coppola
authors: Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, SA, Italy.
authors: Carlo
authors: C
authors: Romano
authors: Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, SA, Italy.
authors: Nicola
authors: N
authors: Capuano
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D017298:Bisoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D001783:Blood Flow Velocity / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine; D017298:Bisoprolol
keywords: Bisoprolol; Cardiology; Coronary artery disease; Coronary flow velocity; Coronary flow velocity reserve; Dipyridamole; Heart rate; Ivabradine