Endothelin receptor antagonists for pulmonary arterial hypertension
Abstract
Background
Pulmonary arterial hypertension (PAH) is a devastating disease, which leads to right heart failure and premature death. Pulmonary arterial hypertension can be classified into two categories: 1) sporadic primary pulmonary hypertension (PPH) or familial PPH and 2) PAH secondary to collagen vascular diseases, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs or toxins, and persistent pulmonary hypertension of the newborn. They have identical pathologic features, a similar clinical course. Endothelin receptor antagonists (ERAs) are a class of potent vasodilators, which could specifically dilate the pulmonary arterial system.
Objectives
To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension.
Search methods
A search was carried out using the CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of August 2004.
Selection criteria
Randomised controlled trials (RCTs) or quasi‐randomised controlled trials involving patients with pulmonary arterial hypertension (PAH) were selected by two reviewers.
Data collection and analysis
Two reviewers independently selected studies; assessed study quality; and extracted data. We analysed outcomes as continuous and dichotomous data.
Main results
We identified three RCTs of short duration (12‐16 weeks), recruiting a total of 423 participants. Two studies compared a non‐selective ERA (bosentan) with placebo and one compared a selective ERA (sitaxsentan) with placebo. Over a 12‐16 week period ERAs improved exercise capacity, improve Borg dyspnoea score, some measures of cardiopulmonary haemodynamics (pulmonary artery pressure, pulmonary vascular resistance, and cardiac index) in symptomatic patients with PAH. The most severe side effect, hepatic toxicity, was not common.
Authors' conclusions
ERAs in conjunction with conventional therapy over 16 weeks can improve exercise capacity, Borg dyspnoea scores and several cardiopulmonary haemodynamics variables in PAH patients. Longer studies are required.
PICOs
Plain language summary
Endothelin receptor antagonists may benefit patients with pulmonary arterial hypertension, at least in the short term. Long term efficacy remains to be confirmed.
Endothelin receptor antagonists, a class of potent vasodilators, have recently been proposed as an alternative to traditional therapies for pulmonary arterial hypertension. This review of trials found that ERAs can improve exercise capacity, symptoms, pulmonary artery pressure, pulmonary vascular resistance, and cardiac index in people with symptomatic pulmonary arterial hypertension over a 12‐16 week period. The most severe potential side effect which affects the liver (hepatic toxicity) was not common in these short‐term trials. Transplantation remains the preferred therapy.
