Early Triple Combination Therapy Including Selexipag Stabilizes Functional Class in PAH/CTEPH

pulmonary hypertension , pah, pulmonary arterial hypertension
Researchers sought to determine whether add-on therapy with the novel oral selective prostacyclin receptor agonist selexipag is beneficial for patients with pulmonary arterial hypertension and distal chronic thromboembolic pulmonary hypertension with intermediate risk.

The early initiation of triple oral combination therapy containing selexipag is associated with improvements in exercise performance and pulmonary hemodynamics, and stabilization in functional class in patients with pulmonary arterial hypertension (PAH) and distal chronic thromboembolic pulmonary hypertension (CTEPH) with intermediate risk, according to study results published in Lung.

Researchers retrospectively reviewed data of patients with PAH/CTEPH (N=23) who had received selexipag in addition to an oral combination therapy at the University Hospital Zurich, Switzerland, between July 2016 and April 2018. The combination therapy was composed of an endothelin receptor antagonist and phosphodiesterase type 5 inhibitor or soluble guanylate cyclase stimulator. Treatment with selexipag was initiated at 200 µg twice daily and increased each week in 200-µg twice-daily increments either until the patient reached the 1600-µg twice-daily maximal dose or until unmanageable adverse effects developed.

At time of study entry, the majority of patients had a New York Heart Association functional class of 3 (n=13) and a mean pulmonary artery pressure of 48 mm Hg. Researchers reviewed changes in New York Heart Association functional class, 6-minute walk distance, N-terminal pro-brain natriuretic peptide, quality of life questionnaires (Cambridge Pulmonary Hypertension Outcome Review and EuroQoL), tricuspid pressure gradient by echocardiography, and cardiopulmonary exercise test parameters (power output and oxygen uptake).

During the treatment period (221 days), patients received an oral triple therapy containing selexipag at a median dose of 2000 µg. From baseline to last follow-up, patients who received the combined treatment regimen experienced stabilization of 6-minute walk distance (median, from 440 to 464 m, respectively), New York Heart Association class (from 3 to 2, respectively), N-terminal pro-brain natriuretic peptide (median, from 326 to 568 ng/L, respectively), tricuspid pressure gradient, power output, and oxygen uptake. There were also observed improvements in quality of life (Cambridge Pulmonary Hypertension Outcome Review, from 3 to 1 [P =.041]; EuroQoL: from 55 to 65 [P =.039]).

Limitations of the study included the small sample size, the relatively short follow-up, and the retrospective nature.

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The researchers wrote that “[f]urther randomized trials should assess the value of triple oral combination therapy in PAH or distal CTEPH not fulfilling all favorable risk criteria.”


Berlier C, Schwarz EI, Saxer S, Lichtblau M, Ulrich S. Real-life experience with selexipag as an add-on therapy to oral combination therapy in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension: a retrospective analysis [published online April 8, 2019]. Lung. doi: 10.1007/s00408-019-00222-7