Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial.

ABSTRACT: BACKGROUND:Right-sided heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Similar to left heart failure, sympathetic overactivation and ?-adrenoreceptor (?AR) abnormalities are found in PAH. Based on successful therapy of left heart failure with ?-blockade, the safety and benefits of the nonselective ?-blocker/vasodilator carvedilol were evaluated in PAH. METHODS:PAH Treatment with Carvedilol for Heart Failure (PAHTCH) is a single-center, double-blind, randomized, controlled trial. Following 1-week run-in, 30 participants were randomized to 1 of 3 arms for 24 weeks: placebo, low-fixed-dose, or dose-escalating carvedilol. Outcomes included clinical measures and mechanistic biomarkers. RESULTS:Decreases in heart rate and blood pressure with carvedilol were well tolerated; heart rate correlated with carvedilol dose. Carvedilol-treated groups had no decrease in exercise capacity measured by 6-minute walk, but had lower heart rates at peak and after exercise, and faster heart rate recovery. Dose-escalating carvedilol was associated with reduction in right ventricular (RV) glycolytic rate and increase in ?AR levels. There was no evidence of RV functional deterioration; rather, cardiac output was maintained. CONCLUSIONS:Carvedilol is likely safe in PAH over 6 months of therapy and has clinical and mechanistic benefits associated with improved outcomes. The data provide support for longer and larger studies to establish guidelines for use of ?-blockers in PAH. TRIAL REGISTRATION:ClinicalTrials.gov NCT01586156FUNDING. This project was supported by NIH R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.

SUBMITTER: Farha S 

PROVIDER: S-EPMC5621927 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature