Analysis Ranks Letairis Best Endothelin Receptor Antagonist for PAH Treatment

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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PAH therapy interactions

Letairis (ambrisentan) was the most efficient, robust therapeutic among endothelin receptor antagonists (ERAs) to treat pulmonary arterial hypertension (PAH), according to a study that compared the drug to three other therapies: Thelin (sitaxsentan), Tracleer (bosentan) and Opsumit (macitentan).

The study, “Comparative efficacy and acceptability of endothelin receptor antagonists for pulmonary arterial hypertension: A network meta-analysis,” appeared in the International Journal of Cardiology.

Letairis, Tracleer and Opsumit are the current main therapeutics for PAH since 2010, when Pfizer voluntarily withdrew Thelin from the market after it discovered that the drug caused fatal liver damage. Nevertheless, researchers decided to include Thelin in their analysis.

ERAs work by relaxing blood vessels and inhibiting their proliferation and remodeling. However, studies comparing the efficacy, tolerability and other clinical outcomes among various ERAs are lacking.

To that end, researchers performed a network meta-analysis comparing all four drugs in order to determine which one is the most efficient in PAH treatment. The team searched in several databases — PubMed, Embase and Cochrane Library – for published studies containing keywords and terms such as pulmonary arterial hypertension, endothelin receptor antagonists, ambrisentan, sitaxsentan, bosentan, macitentan and randomized controlled trial.

From an initial pool of 1,175 articles, only 10 satisfied the pre-determined inclusion criteria. Specifically, that means studies performed as randomized clinical trials in which PAH therapies Tracleer, Thelin, Opsumit and Letairis were compared to placebo controls on the basis of efficacy and/or acceptability.

The meta-analysis showed that while all four drugs had therapeutic effects, Tracleer was found to be the most efficient therapeutical option regarding improvements in 6MWD (six-minute walking distance) and death rates, while ranking second in efficacy for decreasing the risk of clinical worsening.

Although Letairis ranked second in death rates (67.3%) and 6MWD (78.8%), it was close to Tracleer, the top-ranked ERA. Moreover, Letairis was ranked first when evaluating safety outcomes, as it was considered the most favorable regimen to prevent serious adverse effects and discontinuation.

Researchers concluded that Letairis showed a “remarkable performance” and that “future studies adjusting for dosage and different PAH subtypes should be designed to confirm our conclusion. Bosentan also behaved well, but it is not as safe as ambrisentan.”