Triple Therapy Beneficial in Treating Pulmonary Arterial Hypertension


While initial double therapy has proven effective in treating pulmonary arterial hypertension, adding selexipag to the treatment regimen of macitentan and tadalafil could be beneficial in this patient population.

Kelly Chin, MD

Kelly Chin, MD

For patients with pulmonary arterial hypertension, the current recommended treatment is initial double oral combination therapy. However, the advent of initial triple oral combination therapy could be on the horizon.

A team, led by Kelly Chin, MD, UT Southwestern Medical Center, evaluated the efficacy and safety of initial triple oral therapy with selexipag, macitentan and tadalafil compared to initial double oral therapy with macitentan and tadalafil.

The findings from the 247-patient multicenter, double-blind, placebo-controlled, phase 3b TRITON study were planned for presentation at the American Thoracic Society (ATS) 2020 International Conference.

In the trial, the investigators examined newly diagnosed, treatment-naïve PAH patients to either initial triple (n = 123) or initial double therapy (n = 124). Treatment for both groups included macitentan and tadalafil on day 1, with selexipag or placebo added at day 15, which was up-titrated until week 12.

The baseline characteristics were balanced between groups, with a median follow-up of 77.6 and 75.8 weeks in the initial triple and double therapy groups, respectively.

The investigators assessed the efficacy and safety of the treatment in a blinded manner until the last patient randomized completed the week 26 visit.

The team sought a primary endpoint of the change in pulmonary vascular resistance at week 26. expressed as the ratio of baseline.

They also sought secondary endpoints, which were tested hierarchically, including changes in six-minute walk distance (6MWD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 26, time to disease progression until 7 days following the end of the observation period, and the absence of worsening WHOP functional class at week 26.

Overall, the initial triple and initial double therapy improved pulmonary vascular resistance by 54% and 52%, respectively, as well as 6MWD, and NT-proBNP.

The investigators also did no observe worsening in functional class for 99.2% of the initial triple therapy group and 97.5% of patients in the initial double therapy groups.

There was also a 41% reduction in the risk of disease progression with the initial triple therapy group when compared to the initial double therapy group.

There were some adverse events (AE) commonly found in a higher frequency of the triple therapy group, including headaches, diarrhea, nausea, pain in extremities, jaw pain, and vomiting.

However, the proportion of patients suffering from adverse events leading to discontinuation was similar between the 2 treatment groups.

In addition, 2 patients in the initial triple therapy group and 9 participants in the initial double therapy groups died.

“In the TRITON study of newly diagnosed PAH patients, hemodynamics, NT-proBNP and clinical variables were markedly improved with initial triple oral and initial double oral therapy, with no difference between treatment regimens at week 26,” the authors wrote. “Exploratory analysis indicated a signal for improved long-term outcome with initial triple versus initial double therapy. Reported AEs were consistent with known safety profiles for the study medications.”

The study, “Diagnosed Pulmonary Arterial Hypertension (PAH): Results of the Randomized Controlled TRITON Study,” was published online by the ATS International Conference.

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