Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations

Neeraj Dhaun*, Jean-Luc Vachiery, Raymond L. Benza, Robert Naeije, Lie-Ju Hwang, Xuexuan Liu, Simon Teal, David J. Webb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Elevated serum uric acid is detected in pulmonary arterial hypertension (PAR) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAR patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW) and survival.

METHODS: In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2.

RESULTS: Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg and bosentan all reduced serum uric acid (p <0.05). Reduced serum uric acid correlated with increased 6MWD (p = 0.0037).

CONCLUSIONS: Endothelin receptor antagonism reduces serum uric acid in PAR patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.

Original languageEnglish
Pages (from-to)521-527
Number of pages7
JournalJournal of heart and lung transplantation
Volume33
Issue number5
DOIs
Publication statusPublished - 1 May 2014

Keywords

  • 6-minute walk distance
  • bosentan
  • hyperuricemia
  • pulmonary arterial hypertension
  • sitaxentan uric acid
  • CHRONIC KIDNEY-DISEASE
  • CARDIOVASCULAR RISK
  • BOSENTAN THERAPY
  • BLOOD-PRESSURE
  • HYPERURICEMIA
  • MORTALITY
  • ALLOPURINOL
  • SITAXSENTAN
  • PROGRESSION
  • CREATININE

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