Add-on therapy with parenteral prostacyclin analogues in patients with pulmonary arterial hypertension: Insights from the COMPERA registry

Parenteral prostacyclin analogues (PPA) are recommended for pulmonary arterial hypertension (PAH) patients at intermediate-high or high risk, yet supporting evidence remains limited. We retrospectively analyzed pretreated patients with idiopathic/heritable/drug-associated PAH (I/H/D-PAH), connective tissue disease-associated PAH (CTD-PAH), or congenital heart disease-associated PAH (CHD-PAH) from the COMPERA registry who received add-on PPA therapy. Among 495 patients, all pretreated with ≥1 PAH medication, add-on PPA treatment was associated with improvements in 6-minute walk distance, WHO functional class, and NT-proBNP across groups. However, mortality was high: Kaplan-Meier survival estimates at 5 years were 59% in I/H/D-PAH, 59% in CHD-PAH, and 31% in CTD-PAH. Independent predictors of mortality included older age, male sex, CTD, CHD, and intermediate-high or high risk at time of PPA initiation. These findings indicate short-term clinical improvements but high subsequent mortality with add-on PPA therapy in patients with PAH, particularly in those with CTD-PAH, underscoring the need for more effective therapies.