title: Differential effects of nonselective versus selective β-blockers on cardiac sympathetic activity and hemostasis in patients with heart failure.
abstract: Carvedilol, a nonselective β-blocker, may be more effective than the selective β-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either β-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability.
  
  
  METHODS
  In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the β2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis.
  
  
  RESULTS
  (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% ± 3.9% vs. 22.1% ± 2.8%, respectively, P = 0.003), irrespective of β2-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% ± 13% vs. 157% ± 13%, respectively, P = 0.01), irrespective of β2-adrenergic receptor haplotype.
  
  
  CONCLUSIONS
  Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of β2-receptor haplotype status.
authors: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Olav R
authors: OR
authors: de Peuter
authors: Hein J
authors: HJ
authors: Verberne
authors: Wouter E
authors: WE
authors: Kok
authors: Bas
authors: B
authors: van den Bogaard
authors: Marianna C
authors: MC
authors: Schaap
authors: Rienk
authors: R
authors: Nieuwland
authors: Joost C M
authors: JC
authors: Meijers
authors: G Aernout
authors: GA
authors: Somsen
authors: Ad
authors: A
authors: Bakx
authors: Pieter W
authors: PW
authors: Kamphuisen
mesh_terms: D019797:3-Iodobenzylguanidine; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use; D000077261:Carvedilol; D005260:Female; D006239:Haplotypes; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D018579:Patient Selection; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D011877:Radionuclide Imaging; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D000077261:Carvedilol; D019797:3-Iodobenzylguanidine; D008790:Metoprolol
keywords: genetics, coagulation; heart failure; sympathetic nervous system; β-blockers