Document Detail

Frequency of edema in patients with pulmonary arterial hypertension receiving ambrisentan.
MedLine Citation:
PMID:  22858181     Owner:  NLM     Status:  MEDLINE    
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.
Shelley Shapiro; David M Pollock; Hunter Gillies; Noreen Henig; Martine Allard; Christiana Blair; Crystal Anglen; Donald E Kohan
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-08-02
Journal Detail:
Title:  The American journal of cardiology     Volume:  110     ISSN:  1879-1913     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-12     Completed Date:  2013-04-15     Revised Date:  2014-10-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1373-7     Citation Subset:  AIM; IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Age Factors
Analysis of Variance
Confidence Intervals
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Edema / chemically induced*,  epidemiology*,  physiopathology
Follow-Up Studies
Hypertension, Pulmonary / diagnosis,  drug therapy*
Middle Aged
Natriuretic Peptide, Brain / analysis,  drug effects
Phenylpropionates / administration & dosage*,  adverse effects
Pyridazines / administration & dosage*,  adverse effects
Reference Values
Risk Assessment
Safety Management
Severity of Illness Index
Sex Factors
Treatment Outcome
Grant Support
Reg. No./Substance:
0/Phenylpropionates; 0/Pyridazines; 114471-18-0/Natriuretic Peptide, Brain; 177036-94-1/ambrisentan

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