BACKGROUND: Pulmonary arterial hypertension is a devastating disease, which leads to right heart failure and premature death. Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension. OBJECTIVES: To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. SEARCH STRATEGY: We searched CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of Februray 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies, assessed study quality and extracted data. MAIN RESULTS: Five new studies have been added to this updated review, which now includes 11 randomised controlled trials involving 1457 patients. All the trials were of relatively short duration (12 weeks to 6 months). After treatment, patients treated with endothelin receptor antagonists could walk on average 33.7 metres (95% confidence interval [CI] 24.9 to 42.5 metres) further than those treated with placebo in a 6 minute walk test. Endothelin receptor antagonists improved more patients' World Health Organization/New York Heart Association (WHO/NYHA) functional class status than placebo (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.2 to 2.1), and reduced the odds of functional class deterioration compared to placebo (OR 0.26; 95% CI 0.16 to 0.42 ). There was a trend for endothelin receptor antagonists to reduce mortality (OR 0.48; 95% CI 0.21 to 1.09), and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. Hepatic toxicity was not common, and endothelin receptor antagonists were well tolerated in this population. AUTHORS' CONCLUSIONS: Endothelin receptor antagonists can increase exercise capacity, improve WHO/NYHA functional class, prevent WHO/NYHA functional class deterioration, reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III. However, there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension. Efficacy data are strongest in those with idiopathic pulmonary hypertension.
BACKGROUND:Pulmonary arterial hypertension is a devastating disease, which leads to right heart failure and premature death. Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension. OBJECTIVES: To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. SEARCH STRATEGY: We searched CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of Februray 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies, assessed study quality and extracted data. MAIN RESULTS: Five new studies have been added to this updated review, which now includes 11 randomised controlled trials involving 1457 patients. All the trials were of relatively short duration (12 weeks to 6 months). After treatment, patients treated with endothelin receptor antagonists could walk on average 33.7 metres (95% confidence interval [CI] 24.9 to 42.5 metres) further than those treated with placebo in a 6 minute walk test. Endothelin receptor antagonists improved more patients' World Health Organization/New York Heart Association (WHO/NYHA) functional class status than placebo (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.2 to 2.1), and reduced the odds of functional class deterioration compared to placebo (OR 0.26; 95% CI 0.16 to 0.42 ). There was a trend for endothelin receptor antagonists to reduce mortality (OR 0.48; 95% CI 0.21 to 1.09), and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. Hepatic toxicity was not common, and endothelin receptor antagonists were well tolerated in this population. AUTHORS' CONCLUSIONS: Endothelin receptor antagonists can increase exercise capacity, improve WHO/NYHA functional class, prevent WHO/NYHA functional class deterioration, reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III. However, there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension. Efficacy data are strongest in those with idiopathic pulmonary hypertension.
Authors: Elizabeth S Klings; Roberto F Machado; Robyn J Barst; Claudia R Morris; Kamal K Mubarak; Victor R Gordeuk; Gregory J Kato; Kenneth I Ataga; J Simon Gibbs; Oswaldo Castro; Erika B Rosenzweig; Namita Sood; Lewis Hsu; Kevin C Wilson; Marilyn J Telen; Laura M Decastro; Lakshmanan Krishnamurti; Martin H Steinberg; David B Badesch; Mark T Gladwin Journal: Am J Respir Crit Care Med Date: 2014-03-15 Impact factor: 21.405
Authors: Andreas P Kalogeropoulos; Vasiliki V Georgiopoulou; Barry A Borlaug; Mihai Gheorghiade; Javed Butler Journal: Circ Heart Fail Date: 2013-05 Impact factor: 8.790