PMID- 24656288
OWN - NLM
STAT- MEDLINE
DCOM- 20141216
LR  - 20220129
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 33
IP  - 5
DP  - 2014 May
TI  - Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: 
      clinical associations.
PG  - 521-7
LID - S1053-2498(14)00867-5 [pii]
LID - 10.1016/j.healun.2014.01.853 [doi]
AB  - 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.
CI  - Copyright (c) 2014 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Dhaun, Neeraj
AU  - Dhaun N
AD  - Clinical Pharmacology Unit, University of Edinburgh, The Queen׳s Medical Research 
      Institute, Edinburgh, UK. Electronic address: bean.dhaun@ed.ac.uk.
FAU - Vachiery, Jean-Luc
AU  - Vachiery JL
AD  - Pulmonary Hypertension and Heart Failure Clinic, Cliniques Universitaires de 
      Bruxelles - Erasme Hospital, Brussels, Belgium.
FAU - Benza, Raymond L
AU  - Benza RL
AD  - Cardiovascular Research, Allegheny General Hospital, Pittsburgh, Pennsylvania.
FAU - Naeije, Robert
AU  - Naeije R
AD  - Pulmonary Hypertension and Heart Failure Clinic, Cliniques Universitaires de 
      Bruxelles - Erasme Hospital, Brussels, Belgium.
FAU - Hwang, Lie-Ju
AU  - Hwang LJ
AD  - Pfizer Inc New York, New York.
FAU - Liu, Xuexuan
AU  - Liu X
AD  - Quintiles, Durham, North Carolina.
FAU - Teal, Simon
AU  - Teal S
AD  - Pfizer Ltd Tadworth, UK.
FAU - Webb, David J
AU  - Webb DJ
AD  - Clinical Pharmacology Unit, University of Edinburgh, The Queen׳s Medical Research 
      Institute, Edinburgh, UK.
LA  - eng
GR  - FS/13/30/29994/BHF_/British Heart Foundation/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140123
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Isoxazoles)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiophenes)
RN  - 268B43MJ25 (Uric Acid)
RN  - J9QH779MEM (sitaxsentan)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bosentan
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Endothelin Receptor Antagonists/*administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypertension, Pulmonary/blood/*drug therapy/mortality
MH  - Isoxazoles/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Sulfonamides/administration & dosage
MH  - Survival Rate/trends
MH  - Thiophenes/administration & dosage
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States/epidemiology
MH  - Uric Acid/*blood
MH  - Young Adult
OTO - NOTNLM
OT  - 6-minute walk distance
OT  - bosentan
OT  - hyperuricemia
OT  - pulmonary arterial hypertension
OT  - sitaxentan
OT  - uric acid
EDAT- 2014/03/25 06:00
MHDA- 2014/12/17 06:00
CRDT- 2014/03/25 06:00
PHST- 2013/01/29 00:00 [received]
PHST- 2013/11/18 00:00 [revised]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/03/25 06:00 [entrez]
PHST- 2014/03/25 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
AID - S1053-2498(14)00867-5 [pii]
AID - 10.1016/j.healun.2014.01.853 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2014 May;33(5):521-7. doi: 10.1016/j.healun.2014.01.853. 
      Epub 2014 Jan 23.