Endothelin receptor antagonists for pulmonary arterial hypertension

Liu C, Chen J, Gao Y, Deng B, Liu K

Published Online:

July 8, 2009

Endothelin receptor antagonists have recently been proposed as an alternative to traditional therapies for pulmonary arterial hypertension. This updated review included eleven trials and 1457 participants in total. Endothelin receptor antagonists can improve exercise capacity, symptoms, and cardiopulmonary haemodynamic variables in people with symptomatic pulmonary arterial hypertension over a period of 12 weeks to 6 month treatment. There is uncertainty as to whether endothelin receptor antagonists reduce mortality in this population. The most severe potential side-effect was hepatic toxicity which was not common in these short-term trials.

Abstract (click to read)

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.

This record should be cited as:

Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004434. DOI: 10.1002/14651858.CD004434.pub4

Assessed as up to date:

December 4, 2008

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Primary Review Group:

Airways Group

Health topics:

Lungs & airways > Pulmonary hypertension

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Endothelin receptor antagonists for pulmonary arterial hypertension

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