Pulmonary arterial hypertension is a rare and serious disease that can lead to heart failure and early death despite modern treatments. Many patients are treated with a combination of medications targeting different disease pathways, but some continue to have an inadequate response.

Riociguat is a medication that acts on the nitric oxide pathway and may be beneficial in patients who do not respond well to phosphodiesterase-5 inhibitors. In routine clinical practice, some patients receiving triple therapy switch from a phosphodiesterase-5 inhibitor to riociguat.

The REAPPRAISED study evaluates outcomes in patients with pulmonary arterial hypertension who switched to riociguat while receiving triple therapy. This observational study uses data from routine clinical care and does not involve any experimental treatment. The results may help improve understanding of the effectiveness and safety of this treatment strategy 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.

The study population includes adult patients with pulmonary arterial hypertension receiving triple therapy who switched from a phosphodiesterase-5 inhibitor to riociguat in routine clinical practice at a specialized referral center. All patients were followed using retrospective data from medical records to assess clinical outcomes, safety, and treatment persistence. No study-related interventions were performed.