The early anti-oxidant effect of carvedilol predicts the clinical course in congestive heart failure patients.
BACKGROUND
Carvedilol, a beta1 and beta2 as well as an alpha1 adrenoreceptor antagonist with multiple hemodynamic, anti-ischemic and anti-oxidant properties, is widely accepted for the treatment of hypertension and congestive heart failure (CHF). It has been shown to improve morbidity and mortality in CHF.


OBJECTIVE
To assess whether the anti-oxidant effect of carvedilol has an impact on the clinical course in post-myocardial infarction (MI) CHF.


METHODS
Thirty-nine recent MI patients, aged 60.5 +/- 7 years, New York Heart Association functional class (FC) II-III, and left ventricular ejection fraction (LVEF) 29 +/- 3.8%, underwent oxygen free radical (OFR) assessment using the thiobarbituric acid reactive substances, thermochemoluminescence and conjugated dienes methods. OFR was determined at baseline, 1, 3, 12, and 24 h after 3.125, 6.25 and 12.5 mg carvedilol, and after 6 months of treatment. Brain natriuretic peptide (BNP), LVEF, FC change, 6-min walk test (6MW) and quality of life scores were evaluated before and after 6 months.


RESULTS
Two patterns of OFR activity were found. In 29 patients (group 1) a significant and consistent reduction in OFR following administration of each dose of carvedilol was found, significantly correlating with each of the outcome parameters. In ten patients (group 2), no change in OFR was found, nor in any of the other outcomes. At 6 months, FC improved in 23 patients from group 1 (79.3%) and only in one (10%) from group 2 (P<0.01). 6MW increased by more than 10% in group 1 with no change in group 2 (P<0.05). BNP decreased from 397 +/- 36 pg/ml to 171 +/- 15.9 pg/ml (P<0.01) in group 1 compared to 381 +/- 32.5 pg/ml and 405 +/- 36 pg/ml, respectively (P=not significant) in group 2. One year hospital admissions and death rate were significantly higher in group 2.


CONCLUSIONS
The early anti-oxidative effect of carvedilol correlates well with the clinical course and probably predicts it.
Goldhammer
Ehud
E
Department of Cardiology, Bnai-Zion Medical Center and School of Medicine, Technion, Haifa, Israel. egoldh@netvision.net.il
Maor
Irit
I
Shnitzer
Sergei
S
Lanir
Amos
A
Abinader
Edward G
EG
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol