Low-risk status achieved or maintained in minority of patients on PAH combination therapy

In a new study, initial combination therapy for pulmonary arterial hypertension improved functional class and exercise capacity after 6 months, but low-risk status was achieved or maintained in only a minority of patients.

“These disappointing treatment responses appear related to a moderate treatment-induced decrease in [pulmonary vascular resistance], on average no more than 35% (median, 40%), and were predicted either by [European Respiratory Society/European Society of Cardiology] or REVEAL 2.0 scores enriched by a PVR score at initial evaluation,” Roberto Badagliacca, MD, PhD, assistant professor in the department of cardiovascular and respiratory sciences at Sapienza University of Rome, and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

The study enrolled 181 treatment-naive patients with PAH (mean age, 53 years; 120 women). Of these patients, 81% had idiopathic PAH.

All patients had a follow-up right heart catheterization at 6 months after initial combination therapy with endothelin receptor antagonist and PDE5 inhibitor drugs. Sixty-two percent patients started on ambrisentan-tadalafil combination therapy. Researchers performed clinical evaluation and risk assessment using a validated simplified version of the European Respiratory Society and European Society of Cardiology guidelines-derived score and the REVEAL 2.0 score.

The results showed an improvement in 6-minute walk distance (mean distance, 331 m at baseline vs. 384 m at 6 months) and WHO functional class (20.4% were in class I/II at baseline vs. 59.1% at 6 months) after initial combination therapy. Pulmonary vascular resistance decreased by 35% (median, 40%), with a decrease less than 25% in one-third of patients, according to the results.

Age, male sex, pulmonary artery pressure and cardiac index independently predicted the poor hemodynamic response to initial combination therapy. Researchers also noted that right/left ventricular surface area ratio greater than 1 at echocardiography was associated with low tricuspid annular plane systolic excursion of less than 18 mm.

At 6 months, low-risk status was achieved or maintained in 34.8% of patients using the REVEAL 2.0 score and 43.1% of patients using the ERS/ESC score. The researchers noted that adding criteria of poor hemodynamic response improved low-risk status prediction.

“These results suggest that a subpopulation of naive patients who are currently candidates to initial oral combination therapy do not have a good treatment response and need a careful, follow-up and escalation to parenteral prostanoid,” the researchers wrote.