Endothelin receptor antagonists for pulmonary arterial hypertension

Review question

Do endothelin receptor antagonists increase how much a person is capable of exercising (exercise capacity), improve symptoms, or reduce death in people with pulmonary arterial hypertension (PAH)?

Background

Pulmonary arterial hypertension is a devastating disease characterised by an increase in pulmonary vascular resistance which leads to right heart failure and ultimately death.

Endothelin receptor antagonists are a class of strong vasodilators (medications that open (dilate) blood vessels) capable of stopping the process of cell division, which could dilate and result in a favourable pulmonary arterial structural alteration.

Study characteristics

We reviewed the evidence from randomised studies (studies in which people are assigned to one of two or more treatment groups using a random method). After a thorough search and assessment of the medical literature, we identified 17 studies with a total of 3322 participants for inclusion in the review. A vast majority of the participants had PAH without known cause (idiopathic). The evidence is current to November 2020.

Key results

Endothelin receptor antagonists probably increase exercise capacity, improve World Health Organization functional class (a measurement of how severe a person's pulmonary hypertension symptoms are), and may improve death rates and symptoms in people with PAH; however they may also increase the risk of liver damage, although this was rare. The question of the effects of endothelin receptor antagonists on PAH has now likely been answered.

Certainty of the evidence

Overall, the evidence presented is of moderate certainty due to the high occurrence of missing data.

Read the full Cochrane Review here

Non‐invasive ventilation (NIV)

Non‐invasive ventilation (NIV) is a method to assist or replace spontaneous breathing (or normal breathing) with the aid of a machine called a ventilator, using a mask fitted over the nose or both the nose and mouth. NIV can be used chronically at the person's home if they have levels of carbon dioxide in their blood that are persistently too high. We wanted to discover if using chronic NIV at home during the night alongside standard therapy was better or worse than standard therapy alone in people with chronic obstructive pulmonary disease (COPD) who have raised carbon dioxide levels.

Review question

What is the effect of chronic NIV in people with COPD on blood gases (oxygen and carbon dioxide), exercise capacity, quality of life, lung function, respiratory muscle function, COPD exacerbations and admissions, and survival?

Study characteristics

The evidence is current to 21 December 2020. This review included 21 studies. Ten looked at people in a stable phase (stable COPD) and four looked at people shortly after a COPD hospital admission (post‐exacerbation COPD). For our analyses, we used data from 778 people with stable COPD and 364 people with post‐exacerbation COPD.

Results

In all people with COPD who had raised levels of carbon dioxide, chronic NIV for three and 12 months improved blood gases. In stable COPD, chronic NIV also might have improved quality of life, and survival seemed to be better compared to people who were treated with standard care only. There was no relevant benefit of NIV on exercise capacity. People using chronic NIV after a COPD admission experienced less benefit; carbon dioxide levels decreased, the time to the next hospital admission might have been longer when treated with NIV but quality of life and survival were not affected by chronic NIV.

Our confidence in the certainty is good when looking at the blood gases. For the other outcomes, the certainty of the evidence is moderate to very low because the participants and the researcher were aware of the treatment the people received, and due to a wide range in the observed effect. This means that further research might change the results.