title: Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for beta-blocker selection.
abstract: We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating beta-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective beta-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64 +/- 13 years (mean +/- S.D.); range 38-85 years] with CHF. Baseline levels of serum LHP (P<0.002), plasma vWf (P<0.001) and soluble P-selectin (P=0.02), but not fibrinogen (P=0.16), were higher in CHF patients compared with 22 age- and sex-matched healthy controls. After treatment for 2 months, systolic blood pressure fell in both arms of the study (both P<0.01), but there were no statistically significant (defined as P<0.01) decreases in LHP, vWf, fibrinogen or soluble P-selectin levels with either carvedilol or bisoprolol. In conclusion, patients with CHF have increased levels of plasma LHP and vWf, indicating increased oxidative stress and endothelial damage respectively. Contrary to the proposed antioxidative effects of carvedilol, initiating and titrating such therapy did not result in a reduction in levels of LHP in CHF.
authors.affiliation: Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
authors.forename: Bernard S P
authors.initials: BS
authors.lastname: Chin
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gibbs
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D017298:Bisoprolol / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019007:P-Selectin / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D008054:Lipid Peroxides; D019007:P-Selectin; D011412:Propanolamines; D014665:Vasodilator Agents; D014841:von Willebrand Factor; D000077261:Carvedilol; D005340:Fibrinogen; D017298:Bisoprolol