Macitentan Effective in Management of Pulmonary Arterial Hypertension

Zeenat Safdar, MD, MSc, FCCP

New phase 3 data from the SERAPHIN trial found that patients who received the endothelin receptor agonist macitentan were at a reduced risk of a pulmonary arterial hypertension (PAH)-related morbidity event or death.

Additionally, improvements in 6-minute walk distance were recorded in the 2 patients groups featured in the study.

Macitentan 10 mg had been indicated for the treatment of PAH based on data from phase 3 of the trial, which were presented at this year’s CHEST 2021 conference during the session “Macitentan Treatment Effect in Patients with Pulmonary Arterial Hypertension Taking Spironolactone: Post-Hoc Analysis of the Phase 3 Seraphin Trial”.

The study was led by Zeenat Safdar, MD, MSc, FCCP, Houston Methodist Hospital Lung Center.

Though diuretics such as spironolactone had been linked to cardioprotective effects and were frequently used in adjunctive therapy in patients with PAH, there are no established guidelines for the use of diuretics for this patient population.

Likewise, the data were limited on its use in conjunction with other therapies.

In their post-hoc analysis of the SERAPHIN trial, Safdar and colleagues examined the effect of macitentan 10 mg versus placebo in patients who were and were not taking spironolactone at baseline.

The Study

A total of 492 patients were included in the study, all of whom were 12 years or older with PAH.

Patients were randomized 1:1:1 to receive either placebo, macitentan 3 mg once daily or macitentan 10 mg once daily.

A total of 242 patients were included in the macitentan 10 mg group, and 250 were included in the placebo group.

Investigators established the primary endpoint as the time to first PAH-related morbidity event or death from any cause, while a change in 6-minute walking distance from baseline to 6 months was considered the secondary endpoint.

The effect of macitentan 10 mg was evaluated separately in patients who received spironolactone and those who did not, and the effect of macitentan on morbidity/mortality events was assessed using a Cox regression model stratified for key prognostic factors.

Changes in 6-minute walking distance at 3, 6, and 13 months were evaluated using a stratified Wilcoxon rank sum test.

The Findings

The investigators found that patients taking spironolactone had a higher incidence of mortality/morbidity events than those who were not.

However, macitentan 10 mg reduced the risk of such events in both patient gorups, resulting in a 61% reduction in patients taking spironolactone compared to the placebo group.

Additionally, patients taking spironolactone had more marked improvements regarding the secondary endpoint.

Types of adverse events and the event rates were comparable across all groups, with the most common event being the worsening of PAH.

The investigators noted that confounding factors that were not statistically controlled in the analysis might have contributed to the observed outcomes in the subgroups. Despite this, they were confident in the efficacy of macitentan in patients with PAH.

“This post hoc analysis demonstrates that macitentan provides a robust treatment effecting patients with severe PAH who are taking spironolactone, and no new safety signals were discovered among patients taking macitentan and spironolactone,” the team wrote.