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.
Study Type
OBSERVATIONAL
Enrollment
15
Composite Clinical Outcome at 6 Months
Composite clinical outcome assessed at 6 months (24±8 weeks) after the switch to riociguat, defined as achievement of at least two of the following criteria: improvement in six-minute walk distance of at least 10% or 30 meters; World Health Organization functional class I or II; and reduction in BNP levels of at least 30%, in the absence of clinical worsening. Clinical worsening is defined as all-cause mortality, hospitalization due to pulmonary arterial hypertension, or unplanned therapeutic escalation.
Time frame: 6 months (24±8 weeks) after switch
Persistence and Time to Discontinuation of Riociguat
reatment persistence at 6 months and time to discontinuation of riociguat for any reason.
Time frame: Up to 6 months
Safety Outcomes
Occurrence of adverse events, including symptomatic hypotension, syncope, serious adverse events, and treatment interruptions due to adverse events.
Time frame: Up to 6 months
Health Care Utilization
Occurrence of hospitalizations due to pulmonary arterial hypertension and emergency visits in the 6 months before and after the switch to riociguat.
Time frame: 6 months before and 6 months after switch
Functional Changes
Changes in functional level before and after the switch to riociguat.
Time frame: From baseline to 6 months
Risk Stratification (COMPERA 2.0)
Changes in risk stratification using the COMPERA 2.0 score, when sufficient data are available.
Time frame: From baseline to 6 months
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