Initial Triple vs Double Therapy May Improve Long-Term Outcomes in PAH

CT scan PAH
CT scan PAH
In patients newly diagnosed with pulmonary arterial hypertension, initial triple therapy may improve long-term outcomes vs initial double therapy.

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

In patients newly diagnosed with pulmonary arterial hypertension (PAH), emerging data indicate improved long-term outcomes with initial triple (selexipag, macitentan, and tadalafil) vs initial double (macitentan and tadalafil) therapy, according to the results of a phase 3B study (TRITON; Identifier: NCT02558231) intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research is slated to be presented in a virtual format later this year.)

For patients with PAH, initial double oral combination therapy is recommended for treatment. At this time, no data are available on initial triple oral combination therapy. Therefore, researchers evaluated the efficacy and safety of initial triple oral therapy with selexipag, macitentan, and tadalafil compared with initial double oral therapy with macitentan and tadalafil in 247 newly diagnosed, treatment-naive patients with PAH.

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Macitentan and tadalafil were initiated at time of randomization and selexipag/placebo at day 15 (uptitrated until week 12), while efficacy and safety were assessed in a blinded manner until the last patient completed the week 26 visit. The researchers found that initial triple and initial double therapy improved pulmonary vascular resistance (by 54% and 52%), 6-minute walk distance, and N-terminal pro-brain natriuretic peptide, and no worsening in World Health Organization  functional class was seen for 99.2% and 97.5% of patients, respectively, with no difference between groups.

There was also a 41% reduction in the risk of disease progression with initial triple vs initial double therapy (P= .087). Reported adverse events were consistent with known safety profiles for the study medications and the proportions of patients with adverse events leading to selexipag/placebo discontinuation were similar between the groups.

“Exploratory analysis indicated a signal for improved long-term outcome with initial triple vs initial double therapy,” the researchers concluded.


Chin KM, Sitbon O, Doelberg M, et al. Efficacy and safety of initial triple oral versus initial double oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension (PAH): results of the randomized controlled TRITON study. Am J Respir Crit Care Med. 2020;201:A2928.

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