Riociguat in Triple Therapy for Pulmonary Arterial Hypertension in Real-World Practice

Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality despite the use of combination therapy. Triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor is commonly used; however, a subset of patients shows an inadequate clinical response.

Riociguat is a soluble guanylate cyclase stimulator that increases cyclic GMP through both nitric oxide-dependent and nitric oxide-independent mechanisms. Switching from a phosphodiesterase-5 inhibitor to riociguat has shown clinical benefit in selected patients, but data in real-world settings and in patients already receiving triple therapy remain limited.

REAPPRAISED is a single-center, retrospective, observational study conducted in a pulmonary hypertension referral center. The study evaluates clinical outcomes following the switch from a phosphodiesterase-5 inhibitor to riociguat in patients with PAH receiving triple therapy. All treatment decisions were made by the treating physicians as part of routine clinical care. No study-mandated interventions or treatment assignments were performed, and data were obtained from medical records.

Inclusion criteria

• Adults aged 18 years or older.
• Confirmed diagnosis of pulmonary arterial hypertension (Group 1).
• Treatment with triple therapy including an endothelin receptor antagonist, a prostacyclin pathway agent, and a phosphodiesterase-5 inhibitor for at least 12 weeks.
• Switch from a phosphodiesterase-5 inhibitor to riociguat as part of routine clinical care.
• Availability of minimum data to assess the primary outcome at 6 months.

Exclusion criteria

• Concomitant use of phosphodiesterase-5 inhibitors and riociguat.
• Inability to confirm vital status or hospitalization outcomes within 6 months.
• Participation in an interventional clinical trial that mandated the treatment switch.