PAH Experts Discuss Trial-to-Clinic Mismatch in Care

Pulmonary arterial hypertension (PAH) specialists are increasingly candid about a widening gap between how pivotal trials are built and the patients they actually treat, a tension that shaped a recent clinical forum on the 4 therapeutic pathways now available for PAH. Several developments have reshaped access this year: multiple manufacturers began marketing generic macitentan starting in 2025, a transition panelists described as one of the most disruptive their prior-authorization teams have handled¹, even as the fixed-dose macitentan-tadalafil combination’s 90-day free-drug program has been credited elsewhere with helping practices start upfront dual oral therapy without delay.² Separately, the European Respiratory Society formally added the activin signaling inhibitor sotatercept as a strong add-on recommendation for intermediate- and high-risk patients in a September 2026 guideline update.³

Against that backdrop, a panel of pulmonary hypertension specialists gathered for a case-based dinner discussion moderated by Vallerie McLaughlin, MD, who directs the pulmonary hypertension program at the University of Michigan and has practiced in the field for nearly 30 years. The panel included experts from University of Pennsylvania and other community and academic PH specialists.

The conversation arrived at a moment when panelists increasingly described a gap between how PAH trials are constructed and the patients they see in clinic, and between formal risk-stratification algorithms and the “dirty PAH” patients whose comorbid lung or left-heart disease rarely fits cleanly into either. That tension shaped nearly every clinical question the panel worked through, from first-line drug selection to how newer disease-modifying options belong in a treatment sequence that, a generation ago, offered almost nothing.

How Does ‘Dirty PAH’ Complicate Guideline-Based Risk Stratification?

Panelists repeatedly returned to what several called “dirty PAH”—patients with PAH complicated by interstitial lung disease, chronic obstructive pulmonary disease (COPD), or left-heart diastolic dysfunction who rarely match pivotal-trial enrollment criteria.

McLaughlin put the broader problem directly: “I’ll use clean PAH patients with 25 inclusion criteria and 50 exclusion criteria, and the majority of patients that we see in clinic that we’re making these decisions on, that we’re applying these guidelines to would not have met all of those inclusion and exclusion criteria.”

The panel split on risk-assessment tools, with some defaulting to REVEAL because it is built into their EMR and others preferring the 4-strata ESC/ERS framework, several using both when the tools disagree. Six-minute walk distance and NT-proBNP drew open skepticism from multiple panelists, who argued neither reliably drives escalation decisions alone and that trends in oxygen saturation, heart rate response, and right ventricular function on echocardiography are more informative—a debate panelists said is growing more complicated as substantial GLP-1-associated weight loss shifts natriuretic peptide levels independent of right heart function.

How Did Insurance Access, Drug Sequencing Divide the Panel?

On drug sequencing more broadly, panelists described starting most non-high-risk patients on upfront dual combination therapy, typically an endothelin receptor antagonist plus a PDE5 inhibitor, often via the fixed-dose macitentan-tadalafil tablet, though several noted they still stagger the 2 components by a week or 2 in practice even when both are approved together. Patients with overlapping lung disease drove a different calculus: several panelists said they reach for inhaled prostacyclin therapy in that population because it can be titrated faster than oral formulations, reserving parenteral therapy for patients too sick to wait. Insurance access surfaced as a recurring frustration across drug classes, not just newer therapies—panelists described wide inconsistency in which agents get approved and when, including 1 physician denied tadalafil coverage for a newly diagnosed, severely ill patient the same day a costlier add-on therapy was approved for a different patient. Multiple panelists credited dedicated pharmacy and prior-authorization staff, rather than any single clinical strategy, as the single biggest factor in getting patients onto guideline-recommended combination therapy.

References

1. Generic Opsumit Availability. Drugs.com. Accessed September 21, 2026. https://www.drugs.com/availability/generic-opsumit.html

2. PAH in 2026: Algorithm Shifts and Real-World Gaps. HCPLive. Accessed September 21, 2026. https://hcplive.com/view/pah-2026-algorithm-shifts-prostacyclin-new-role-real-world-gaps

3. ERS Adds Sotatercept to Pulmonary Arterial Hypertension Treatment Guidelines. Pharmacy Times. Published September 16, 2026. Accessed September 21, 2026. https://pharmacytimes.com/view/ers-adds-sotatercept-to-pah-treatment-guidelines