Experts Discuss PAH Treatment Selection and Access

Clinicians treating pulmonary arterial hypertension (PAH) now choose among therapies across 4 pathways, and recent developments have added options at several points in care. These include FDA approval of a once-daily single-tablet combination of macitentan and tadalafil, supported by the phase 3 A DUE trial, and a September 2026 European Respiratory Society (ERS) guideline update that incorporates sotatercept, the first activin signaling inhibitor.¹⁻³ In practice, choices among these agents increasingly reflect risk assessment, comorbidities, payer coverage, and patient resources.

During the CHEST 2026 Annual Meeting in Phoenix, Arizona, Jean Elwing, MD, director of the Pulmonary Hypertension Program at the University of Cincinnati, moderated a clinical forum on PAH treatment. Participants included pulmonologists and pulmonary critical care physicians from academic and community programs in Oklahoma, Ohio, Florida, North Carolina, California, Michigan, and Arizona, including 1 who also treats pediatric patients. The discussion covered initial therapy, guideline interpretation, prostacyclin use, and barriers to access and adherence.

Upfront Combination Therapy and Payer-Driven Drug Choice

Participants said most newly diagnosed patients without high-risk features receive upfront dual therapy with a phosphodiesterase 5 (PDE5) inhibitor and an endothelin receptor antagonist (ERA), consistent with the AMBITION approach.⁴ Several said the specific agents depend on coverage, with 1 participant describing Medicaid requirements for sildenafil and ambrisentan and others reporting payer-mandated switches to generic macitentan. Some participants described using low-cost online pharmacies for underinsured patients.

Participants favored once-daily dosing and single-tablet combinations for adherence, particularly in young adults, though several said coverage limits access. Others described deviating from routine dual therapy, starting monotherapy in older patients with suspected left heart disease or in hospitalized patients unlikely to return for follow-up. Most participants said they use REVEAL 2.0 at diagnosis and noted that multiparametric tools may not capture right ventricular (RV) dysfunction, so imaging informs their escalation decisions.

Interpreting the 2026 ERS Guideline for High-Risk PAH

Participants debated the updated ERS treatment algorithm, which several said could be misread as favoring sotatercept over parenteral prostacyclins in high-risk patients. Some said the figure diverges from the more detailed guideline text, and 1 participant suggested "consider" would be more appropriate wording given emerging data for other agents, such as topline results for the investigational oral prostacyclin receptor agonist ralinepag. Others said a simpler algorithm may help community clinicians in rural areas who cannot manage infusion therapy.

Participants also noted that European access to prostacyclin pathway agents is narrower than in the US, which may shape how the algorithm is structured. Several said US recommendations should reflect the broader range of available therapies.

Prostacyclin Use and Activin Signaling Inhibition

Participants said they start parenteral prostacyclins less often than in the past but still reserve them for patients with severe RV dysfunction, very low cardiac index, syncope, pregnancy, or an urgent need for hemodynamic improvement. Several described infusion therapy as induction rather than lifelong treatment, and 1 participant said the immediate response to parenteral therapy remains valuable for acute salvage. Inhaled treprostinil titrated to higher doses was described as an alternative for some intermediate-high-risk patients, while oral prostacyclin pathway agents were most often used for de-escalation, with participants noting that oral treprostinil demands considerable diligence even though patients prefer oral therapy.

Participants said sotatercept has changed their practice most in high-risk patients and in prevalent intermediate-high-risk patients with persistent RV dysfunction. Several cited more variable responses than with established therapies, limited long-term data, and cases of pulmonary arteriovenous malformations and hypoxemia, and 1 participant said they prefer prostacyclins in high-risk patients with scleroderma given the side effect profile. Others cautioned against de-escalating too quickly in patients who have not achieved normal imaging and hemodynamics.

Adherence and Access Barriers in PAH Care

Participants identified loss of insurance coverage, unreported adverse effects, and limited follow-up contact as leading causes of nonadherence. To assess adherence, participants described asking how many of a week's doses patients actually take, reviewing pharmacy dispense histories, and normalizing missed doses so patients answer honestly. Several said therapy should not be escalated until adherence is addressed.

Participants also cited state licensing restrictions on telehealth as a barrier for patients who live far from PH centers, and several said affordability will determine whether newer therapies reach the patients who need them. "We could talk forever about why to choose one over another in certain populations. But I think we just have to recognize we have choices and we choose them based on our patients' needs," Elwing said.

References

1. Grünig E, Jansa P, Fan F, et al. Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83(4):473-484. doi:10.1016/j.jacc.2023.10.045

2. Kovacs G, Zeder K, Humbert M, et al. European Respiratory Society clinical practice guidelines update for the treatment of pulmonary arterial hypertension. Eur Respir J. Published online September 7, 2026. doi:10.1183/13993003.01178-2026

3. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558

4. Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834-844. doi:10.1056/NEJMoa1413687