title: Differential effects of heart rate reduction by atenolol or ivabradine on peripheral endothelial function in type 2 diabetic patients.
abstract: OBJECTIVE
  To assess whether reduction of heart rate (HR) has beneficial effects on endothelial function in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Randomised, double-blind, placebo-controlled study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  66 T2DM patients without overt cardiovascular disease.
  
  
  METHODS
  Patients were randomised to receive for 4 weeks, in addition to their standard therapy, one of the following treatments: atenolol (25 mg twice daily), ivabradine (5 mg twice daily) or placebo (1 tablet twice daily).
  
  
  METHODS
  Systemic endothelial function, assessed by flow-mediated dilation (FMD); endothelium-independent vasodilation, assessed by nitrate-mediated dilation (NMD); cardiac autonomic function, assessed by HR variability (HRV).
  
  
  RESULTS
  61 patients completed the study (19, 22 and 20 patients in atenolol, ivabradine and placebo groups, respectively). Compared with baseline, HR was similarly reduced by atenolol (87±13 vs 69±9 bpm) and ivabradine (86±12 to 71±9 bpm), but not by placebo (82±10 vs 81±9 bpm) (p<0.001). FMD improved at follow-up in the atenolol group (4.8±1.7 vs 6.4±1.9%), but not in the ivabradine group (5.2±2.5 vs 4.9±2.2%) and in the placebo group (4.8±1.5 vs 4.7±1.7%) (p<0.01). NMD did not change significantly in any group. HRV parameters did not change in the placebo group; they, instead, consistently increased in the atenolol, whereas a mild increase in SDNNi was only observed in the ivabradine group. A significant correlation was found in the atenolol group between HR and FMD changes (r=-0.48; p=0.04).
  
  
  CONCLUSIONS
  Despite a comparable reduction in HR, atenolol, but not ivabradine, improved FMD in T2DM patients suggesting that changes in HR are by themselves unlikely to significantly improve endothelial function.
authors.affiliation: Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nerla
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Franco
authors.forename: Maria
authors.initials: M
authors.lastname: Milo
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Tarzia
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Sarullo
authors.forename: Angelo
authors.initials: A
authors.lastname: Villano
authors.forename: Giulio
authors.initials: G
authors.lastname: Russo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stazi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ghirlanda
authors.forename: Gaetano Antonio
authors.initials: GA
authors.lastname: Lanza
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
mesh_terms: D001262:Atenolol / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D054815:Cyclic Nucleotide-Gated Cation Channels; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D004311:Double-Blind Method; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D013565:Sympatholytics; D000077550:Ivabradine; D001262:Atenolol