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J Heart Lung Transplant. 2014 May;33(5):521-7. doi: 10.1016/j.healun.2014.01.853. Epub 2014 Jan 23.

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

Author information

1
Clinical Pharmacology Unit, University of Edinburgh, The Queen׳s Medical Research Institute, Edinburgh, UK. Electronic address: bean.dhaun@ed.ac.uk.
2
Pulmonary Hypertension and Heart Failure Clinic, Cliniques Universitaires de Bruxelles - Erasme Hospital, Brussels, Belgium.
3
Cardiovascular Research, Allegheny General Hospital, Pittsburgh, Pennsylvania.
4
Pfizer Inc New York, New York.
5
Quintiles, Durham, North Carolina.
6
Pfizer Ltd Tadworth, UK.
7
Clinical Pharmacology Unit, University of Edinburgh, The Queen׳s Medical Research Institute, Edinburgh, UK.

Abstract

BACKGROUND:

Elevated serum uric acid is detected in pulmonary arterial hypertension (PAH) 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 PAH 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 PAH 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.

KEYWORDS:

6-minute walk distance; bosentan; hyperuricemia; pulmonary arterial hypertension; sitaxentan; uric acid

PMID:
24656288
DOI:
10.1016/j.healun.2014.01.853
[Indexed for MEDLINE]
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