title: Ivabradine therapy to unmask heart rate-independent effects of β-blockers on pulse wave reflections.
abstract: BACKGROUND
  Prior studies suggest that β-blockers lead to increased pulse wave reflections, thereby negating the blood pressure lowering effects on cardiovascular mortality. Parts of these effects may be induced by the heart rate reduction under β-blockade. The aim of this study was to unmask heart rate-independent effects of β-blockade on pulse wave reflections by switching therapy from β-blockers to ivabradine, an I f channel inhibitor without impact on systemic hemodynamics.
  
  
  METHODS
  14 male patients (age 61 ± 3 years, LVEF 62 ± 1 %) with arterial hypertension and coronary artery disease (CAD) under chronic β-blocker therapy at moderate dosage and additional renin-angiotensin system-blocking therapy were included. We determined radial augmentation index (rAI) by radial applanation tonometry in patients under β-blockade both at rest and during early recovery after exercise. β-Blockers were then replaced by ivabradine. Six weeks later, patients were re-tested at rest and after exercise under ivabradine therapy.
  
  
  RESULTS
  Mean heart rate (68 ± 3 vs. 63 ± 3 bpm; p = ns) and resting mean arterial pressure (98 ± 2 vs. 98 ± 2 mmHg; p = ns) were not different between β-blocker or ivabradine therapy, respectively. The rAI remained unchanged after switching therapy from β-blocker to ivabradine (86 ± 2 vs. 84 ± 4 %; p = ns). Post exercise, the rAI revealed an identical decrease in both groups (-7.2 ± 2.4 vs. -5.4 ± 2.5 %, p = ns). The increase in heart rate between resting conditions and early recovery post exercise was inversely correlated with the decrease of rAI under β-blockade (r = -0.70; p < 0.01) and showed a trend towards correlation under ivabradine (r = -0.52; p = 0.07).
  
  
  CONCLUSIONS
  In men at the age of 60 years and CAD, β-blockade does not exert heart rate-independent, pleiotropic effects on peripheral pulse wave reflections, both at rest or after exercise. Our results fit well within recent studies, demonstrating the fundamental influence of heart rate on rAI.
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany, fischer-rasokat@gmx.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Fischer-Rasokat
authors.forename: Jörg
authors.initials: J
authors.lastname: Honold
authors.forename: Denise
authors.initials: D
authors.lastname: Lochmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.forename: Jürgen
authors.initials: J
authors.lastname: Leick
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
authors.forename: Ioakim
authors.initials: I
authors.lastname: Spyridopoulos
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D000077550:Ivabradine