Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von Willebrand factor in chronic heart failure--a COMET substudy.
BACKGROUND
In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure.


METHODS
We recruited 260 patients (134 on carvedilol, 126 on metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of tPA and PAI-1and percent of VWF were measured at baseline and after one and two years of treatment.


RESULTS
Plasma tPA, PAI-1 and VWF were similar between treatment groups at baseline and no significant differences between groups emerged after one or two years of treatment. In paired analyses in patients assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 microg/l at two years (p=0.034) and of VWF decreased from baseline to one year (240 vs. 218%, p=0.023) in patients assigned to carvedilol but were not reduced at any time in patients assigned to metoprolol. Plasma tPA increased over time in both treatment groups (p=0.013 and 0.027 respectively).


CONCLUSIONS
We found no significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1 and VWF. Comparison over time within treatment groups suggested that PAI-1 and VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is not proved but this may reflect an inadequate sample size rather than lack of an effect.
Boman
Kurt
K
Department of Medicine, Skellefteå County Hospital, Skellefteå, Umeå University, Sweden. kurt.boman@vll.se
Jansson
Jan-Håkan
JH
Nilsson
Torbjörn
T
Swedberg
Karl
K
Cleland
John G F
JG
Poole-Wilson
Philip
P
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018401:Sample Size; D013548:Sweden; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D017395:Plasminogen Activator Inhibitor 1; D011412:Propanolamines; D014841:von Willebrand Factor; D000077261:Carvedilol; D010959:Tissue Plasminogen Activator; D008790:Metoprolol