#5-35E. Once-Daily Ralinepag Redefines Clinical Progression in Pulmonary Arterial Hypertension (Lancet, 2026)

How should we optimize prostacyclin pathway escalation in patients with pulmonary arterial hypertension who are already stable on background dual therapy? In the landmark ADVANCE OUTCOMES trial, a randomised, double-blind, placebo-controlled, phase 3 study, researchers evaluated the efficacy of ralinepag, a novel once-daily oral selective prostacyclin IP receptor agonist. Adding ralinepag to contemporary background treatments reduced the risk of first clinical worsening by an impressive 55% (hazard ratio 0.45), while significantly improving exercise capacity and heart strain markers. However, a critical caveat for clinicians is the high treatment discontinuation rate of 19% due to adverse events in the ralinepag group compared to only 3% in the placebo group, which potentially threatens the trial's blinding due to predictable prostacyclin-related side effects. For practicing physicians, these findings underscore the potential of early, oral-based triple combination therapy to halt disease progression, though optimizing titration and managing tolerability in real-world clinical practice remains key to unlocking ralinepag's full clinical benefits.

Citation: McLaughlin VV, et al. Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study. Lancet. 2026. DOI: 10.1016/S0140-6736(26)01011-1 URL: https://doi.org/10.1016/S0140-6736(26)01011-1

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