Treat Early, Treat Hard: Redefining the Modern PAH Treatment Paradigm

The past several years have marked a clear inflection point in pulmonary arterial hypertension (PAH), with 2024 initiating a new phase of therapeutic expansion that has continued to unfold through 2025 and into 2026. After decades of incremental progress within established drug classes, the field has entered a period defined by diversification, in both mechanism and treatment strategy, reshaping how clinicians think about disease modification, escalation, and long-term management.

That shift gained momentum with landmark approvals in 2024, including sotatercept (Winrevair), the first therapy to target the activin signaling pathway, and the first once-daily fixed-dose combination of macitentan and tadalafil, marketed as Opsynvi. These approvals introduced not only new mechanisms and simplified regimens, but also a broader rethinking of how therapies can be layered earlier and more efficiently. In 2025, momentum continued with the FDA approval of inhaled treprostinil powder (Yutrepia) for PAH both alone and associated with interstitial lung disease, expanding prostacyclin therapy through a novel delivery approach designed to optimize pulmonary deposition.

As these advances accumulate, the PAH treatment landscape in 2025 and beyond reflects a growing emphasis on flexibility, durability, and individualized care. The expanding range of targets, formulations, and combinations has shifted clinical conversations toward how best to integrate newer agents alongside established pathways, how to balance efficacy with treatment burden, and how evolving evidence may redefine long-term therapeutic goals in a disease once constrained by limited options.

At a recent clinical forum convened by HCPLive in New York City, a group of pulmonologists and cardiologists led by Roxana Sulica, MD, a pulmonary medicine specialist at NYU Langone, gathered to discuss the evolving treatment field of PAH.

Throughout the forum, participants emphasized the critical importance of precise diagnosis and expert interpretation of hemodynamic data, particularly in an era where mixed or overlapping forms of pulmonary hypertension are increasingly encountered. Accurate classification, thoughtful use of right heart catheterization, and contextual interpretation of pulmonary arterial wedge pressure (PAWP) and other measurements were repeatedly highlighted as foundational to effective treatment decisions. The group agreed that while guidelines provide an essential framework, PAH management often requires nuanced clinical judgment that extends beyond algorithmic care.

“[Treating patients] is certainly a gestalt and I always said that guidelines are guides, not replacements for the prefrontal cortex of the doctor. And it was in the Blue journal (American Journal of Respiratory Cell and Molecular Biology), that article written by cardiologists [about measuring PAWP], - the title of the article I found fabulous, is, "This Patient Needs a Doctor, Not a Guideline",” Sulica said during the forum.

:I tend to repeat more often than the guidelines say… I tend to believe the cath, and the echo more than the patient. And I did fool myself in my youth a couple of times when I believed the patient and that was the wrong- hence 90%-10% shared decision-making,” one panelist said.

The discussion also reflected a broad consensus that modern PAH treatment is moving toward earlier, more aggressive, and more comprehensive therapy. Combination regimens targeting multiple pathways, judicious use of prostacyclin therapies for higher-risk patients, and the integration of newer disease-modifying agents were all framed as part of an evolving strategy focused on preserving right ventricular function and improving long-term outcomes.

“So you guys are OK if the patient doesn't follow-up their stuff and the drugs stop? Are you OK with that?” a panelist asked.

“If I feel like I have given them the data, the information, then it’s my responsibility to say to the patient, ‘it has to be on you, and it's important to do it, because it's dangerous to stop the medication,” another answered.

Alongside therapeutic advances, the forum highlighted persistent systemic challenges, including access to specialty care, referral delays, and care coordination, that continue to influence real-world outcomes and underscore the need for centralized expertise in PAH management.