PMID- 22858181
OWN - NLM
STAT- MEDLINE
DCOM- 20130415
LR  - 20220409
IS  - 1879-1913 (Electronic)
IS  - 0002-9149 (Print)
IS  - 0002-9149 (Linking)
VI  - 110
IP  - 9
DP  - 2012 Nov 1
TI  - Frequency of edema in patients with pulmonary arterial hypertension receiving 
      ambrisentan.
PG  - 1373-7
LID - S0002-9149(12)01634-7 [pii]
LID - 10.1016/j.amjcard.2012.06.040 [doi]
AB  - Edema is a common side effect of endothelin receptor antagonists. Ambrisentan is 
      an endothelin type A-selective endothelin receptor antagonist approved for the 
      treatment of pulmonary arterial hypertension. We examined the clinical outcomes 
      of patients who developed edema with and without ambrisentan treatment in 2 phase 
      III, randomized placebo-controlled trials, ambrisentan for the treatment of 
      pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial 
      hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy 
      (ARIES) study 1 and 2 (ARIES-1 and ARIES-2) (n = 393). Edema-related adverse 
      events were extracted using broad adverse event search terms. The present post 
      hoc analysis included 132 placebo patients and 261 ambrisentan patients. Of these 
      patients, 14% of the placebo patients and 23% of the ambrisentan patients 
      experienced edema-related adverse events. Overall, the patients who experienced 
      edema tended to have a worse baseline World Health Organization (WHO) functional 
      class (edema 76%, WHO functional class III-IV; no edema 56%, WHO functional class 
      III-IV). In the ambrisentan patients, those with edema were older (mean age 58 +/- 
      13 years) and heavier (mean weight 75 +/- 19 kg) than those without edema (mean age 
      49 +/- 15 years; mean weight 70 +/- 17 kg). At week 12 of treatment, the ambrisentan 
      patients had significantly increased their 6-minute walk distance (6MWD) by 34.4 
      m compared to the placebo patients in whom the 6MWD had deteriorated by -9.0 m (p 
      <0.001). Among the ambrisentan patients, those without edema had a 6MWD increase 
      of 38.9 m and those with edema had a 6MWD increase of 19.4 m. Ambrisentan 
      significantly improved the brain natriuretic peptide levels by -34% compared to 
      the brain natriuretic peptide levels in the placebo group that had worsened by 
      +11% (p <0.001). Ambrisentan reduced the brain natriuretic peptide concentrations 
      similarly in patients with and without edema. In conclusion, the present 
      subanalysis of patients with pulmonary arterial hypertension has revealed that 
      ambrisentan therapy provides clinical benefit compared to placebo, even in the 
      presence of edema.
CI  - Published by Elsevier Inc.
FAU - Shapiro, Shelley
AU  - Shapiro S
AD  - West Los Angeles Veterans Affairs Healthcare System, David Geffen University of 
      California, Los Angeles, School of Medicine, Los Angeles, California, USA. 
      Sshapiro@ucla.edu
FAU - Pollock, David M
AU  - Pollock DM
FAU - Gillies, Hunter
AU  - Gillies H
FAU - Henig, Noreen
AU  - Henig N
FAU - Allard, Martine
AU  - Allard M
FAU - Blair, Christiana
AU  - Blair C
FAU - Anglen, Crystal
AU  - Anglen C
FAU - Kohan, Donald E
AU  - Kohan DE
LA  - eng
GR  - R01 DK069392/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120802
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyridazines)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - HW6NV07QEC (ambrisentan)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Analysis of Variance
MH  - Confidence Intervals
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Edema/*chemically induced/*epidemiology/physiopathology
MH  - Familial Primary Pulmonary Hypertension
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypertension, Pulmonary/diagnosis/*drug therapy
MH  - Incidence
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/analysis/drug effects
MH  - Phenylpropionates/*administration & dosage/adverse effects
MH  - Pyridazines/*administration & dosage/adverse effects
MH  - Reference Values
MH  - Risk Assessment
MH  - Safety Management
MH  - Severity of Illness Index
MH  - Sex Factors
MH  - Treatment Outcome
PMC - PMC4167616
MID - NIHMS626768
EDAT- 2012/08/04 06:00
MHDA- 2013/04/16 06:00
PMCR- 2014/09/18
CRDT- 2012/08/04 06:00
PHST- 2012/03/24 00:00 [received]
PHST- 2012/06/13 00:00 [revised]
PHST- 2012/06/13 00:00 [accepted]
PHST- 2012/08/04 06:00 [entrez]
PHST- 2012/08/04 06:00 [pubmed]
PHST- 2013/04/16 06:00 [medline]
PHST- 2014/09/18 00:00 [pmc-release]
AID - S0002-9149(12)01634-7 [pii]
AID - 10.1016/j.amjcard.2012.06.040 [doi]
PST - ppublish
SO  - Am J Cardiol. 2012 Nov 1;110(9):1373-7. doi: 10.1016/j.amjcard.2012.06.040. Epub 
      2012 Aug 2.