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Carvedilol does not improve exercise performance in Fontan patients

Presented by
Dr Ryan Butts, University of Texas Southwestern, Dallas, USA
AHA 2019
Dr Ryan Butts (University of Texas Southwestern, Dallas, USA) presented the results of a double-blind, placebo-controlled, cross-over trial of carvedilol in single-ventricle patients with Fontan physiology [1]. The rationale behind the trial was that beta-blockers may ameliorate the increased circulating catecholamines in these patients and, consequently, improve their exercise performance; however, no difference was observed between the 2 arms.

The study enrolled 26 single-ventricle patients between 10-35 years old with a previous Fontan operation who were able to complete a maximal exercise test (respiratory exchange ratio [RER] >1.0). Two 12-week treatment arms were separated by a period of 6 weeks for drug washout. Exercise testing was performed at the beginning and end of each treatment arm. Study drug was increased to a goal maximum dose (0.2-0.3 mg/kg/dose twice daily). The primary study outcome was an improvement in peak oxygen consumption/kg (pVO2) from the baseline measurement.

Out of the 26 participants, 23 were able to complete the study. In the carvedilol arm, 4 subjects were unable to reach the maximum dose, as compared with a single participant in the placebo arm (P=0.14). The primary outcome was not met; the mean change in pVO2 between treatments was not different (-2.1 mL/kg/min in the carvedilol arm vs -1.42 in the placebo arm; P=0.28). The peak heart rate decreased in subjects taking carvedilol (P<0.01) leading to a subsequent increase in peak oxygen pulse (P<0.01). No differences were reported for ventilatory efficiency (slope of VE/VCO2 curves), oxygen uptake efficiency, or maximum work performed. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels increased with carvedilol (mean +23.77 pg/mL) compared with the placebo arm (mean -5.37 pg/mL; P=0.03).

No serious adverse events were observed in the carvedilol arm. Dr Butts concluded that carvedilol had a safe tolerability profile in the majority of subjects with Fontan physiology, despite not being associated with improved exercise performance. Furthermore, carvedilol was associated with mildly increased levels of NT-proBNP. In brief, this study suggests that there is no indication for carvedilol in healthy Fontan patients. The role of potential carvedilol therapy in Fontan patients with heart failure may warrant additional research.

1. Butts RJ, et al. Carvedilol Does Not Improve Exercise Performance in Fontan Patients: Results of a Cross Over Trial. FS.AOS.04, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.

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