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

doi:10.1016/j.healun.2014.01.853

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 journal › Article › peer-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 language	English
Pages (from-to)	521-527
Number of pages	7
Journal	Journal of heart and lung transplantation
Volume	33
Issue number	5
DOIs	https://doi.org/10.1016/j.healun.2014.01.853
Publication status	Published - 1 May 2014

Keywords / Materials (for Non-textual outputs)

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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10.1016/j.healun.2014.01.853

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@article{33053c5e51904a599a0cc5dfeb72afea,

title = "Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: Clinical associations",

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.",

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",

author = "Neeraj Dhaun and Jean-Luc Vachiery and Benza, {Raymond L.} and Robert Naeije and Lie-Ju Hwang and Xuexuan Liu and Simon Teal and Webb, {David J.}",

year = "2014",

month = may,

day = "1",

doi = "10.1016/j.healun.2014.01.853",

language = "English",

volume = "33",

pages = "521--527",

journal = "Journal of heart and lung transplantation",

issn = "1053-2498",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Endothelin antagonism and uric acid levels in pulmonary arterial hypertension

T2 - Clinical associations

AU - Dhaun, Neeraj

AU - Vachiery, Jean-Luc

AU - Benza, Raymond L.

AU - Naeije, Robert

AU - Hwang, Lie-Ju

AU - Liu, Xuexuan

AU - Teal, Simon

AU - Webb, David J.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - 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.

AB - 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.

KW - 6-minute walk distance

KW - bosentan

KW - hyperuricemia

KW - pulmonary arterial hypertension

KW - sitaxentan uric acid

KW - CHRONIC KIDNEY-DISEASE

KW - CARDIOVASCULAR RISK

KW - BOSENTAN THERAPY

KW - BLOOD-PRESSURE

KW - HYPERURICEMIA

KW - MORTALITY

KW - ALLOPURINOL

KW - SITAXSENTAN

KW - PROGRESSION

KW - CREATININE

U2 - 10.1016/j.healun.2014.01.853

DO - 10.1016/j.healun.2014.01.853

M3 - Article

SN - 1053-2498

VL - 33

SP - 521

EP - 527

JO - Journal of heart and lung transplantation

JF - Journal of heart and lung transplantation

IS - 5

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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