PAH Undertreatment Common in US, Europe, and Japan, Survey Shows

Most people with pulmonary arterial hypertension (PAH) are not receiving combination therapy, even when they have advanced disease, according to a new report.

The findings — based on real-world evidence from seven countries — suggest a gap between guideline recommendations and real-world practice. The data were published in Advances in Therapy.

PAH management guidelines vary from jurisdiction to jurisdiction, explained corresponding author R.J. White, M.D., Ph.D., of the University of Rochester Medical Center, and colleagues. European guidelines recommend that patients with low- or intermediate-risk PAH be given combination therapy with an endothelin receptor agonist (ERA) and an phosphodiesterase 5 inhibitor (PDE5i).

In patients with high-risk disease, an additional therapy — parenteral prostacyclin — is recommended. In Japan, guidelines recommend monotherapy for low-risk patients, and combination therapy for intermediate- or high-risk patients. The American College of Chest Physicians recommends patients with World Health Organization (WHO) Class I disease be monitored, those with class II or III disease be treated combination ERA/PDE5i therapy, and those with class IV disease be treated with parenteral prostacyclin.

Yet, White and colleagues said such guidelines are often not followed.

“The complex evaluation necessary for PAH and the varying reimbursement for expensive treatments likely create an even greater disconnect between consensus guidelines and real-world prescribing,” they wrote.

The investigators decided to survey physicians in the U.S., five European countries and Japan to learn about the PAH patients they are seeing, their treatment selection, and the reasons behind those selections. Survey responses were collected between March and August 2022. In total, 293 physicians provided information related to 1,173 patients. About 40% of physicians surveyed were pulmonologists, and a similar number were cardiologists. More than half (55%) of physicians said they spent the majority of their time at university or teaching hospitals, and just under one-half said they were affiliated with a PAH center or program specializing in PAH.The patients had an average age of 58.7 years, and just over half of the patients (54.6%) were female.

Nine in 10 patients (91.2%) had received — or were still receiving — therapy for PAH.

“About three-quarters of the cohort were still taking the initial treatment strategy: for this group, 54% were prescribed monotherapy and 32% combination therapy; 15% of patients received supportive therapy alone,” White and colleagues reported.

The investigators found significant regional differences; 94.6% of patients in France were receiving PAH-specific treatment compared with 82.0% in the United States, the lowest rate of any country.

In addition, only 23.8% of American patients were receiving combination therapy, again the lowest rate of the surveyed countries. German clinicians, on the other hand, reported prescribing combination therapy to 36.5% of their patients with PAH.

In general, combination therapy use rates increased as WHO functional class increased. Yet, the authors said only 51% of patients with class III disease were receiving combination therapy.

When asked about their treatment choices, it was unusual for physicians to cite the guidelines, White and his co-authors wrote. “Consistent with our data that there was a substantial degree of divergence from PAH treatment guidelines, ‘to follow guidelines’ was a relatively unusual reason for prescribing a treatment regimen (less than  30%)," they wrote.

When clinicians carried out guideline-recommended PAH assessments, however, they were more likely to follow treatment guidelines by prescribing combination therapy.

In cases where patients were receiving monotherapy, clinicians tended to cite slow disease progression as the reason behind their prescription choices. That was true regardless of whether the physician was a PAH specialist and regardless of whether the patient was being treated at a regional hospital or at an academic medical center.

White and colleagues said the data suggest a “concerning” degree of undertreatment of patients with PAH in real-world practice.

“Many patients were not receiving PAH-specific treatment or were receiving monotherapy when their functional classification would suggest combination treatment was indicated,” they wrote.

They said more aggressive approaches ought to be adopted earlier for high-risk patients in order to ensure patients have the best chance at long-term survival.