The early anti-oxidant effect of carvedilol predicts the clinical course in congestive heart failure patients

Background Carvedilol, a 01 and 02 as well as an a, 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. Objectives 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 Ml 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 24h after 3.125, 6.25 and 12.5mg 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 (110%) from group 2 (P < 0.01). 6MW increased by more than 10% in group I 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.