Long-Term Outcomes of Selexipag in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Schistosomiasis-associated pulmonary arterial hypertension (PAH-Sch) is a prevalent cause of pulmonary arterial hypertension in endemic regions and is associated with significant morbidity and premature mortality. Despite advances in targeted therapies for pulmonary arterial hypertension, patients with PAH-Sch remain underrepresented in long-term studies, particularly in real-world clinical settings.

Selexipag, an oral selective prostacyclin IP receptor agonist, has demonstrated clinical and hemodynamic benefits in pulmonary arterial hypertension. Following its incorporation into routine clinical practice in Brazil, selexipag has been increasingly used in eligible patients with PAH-Sch. However, evidence regarding its long-term outcomes in this specific population is limited.

PROPULSE-Sch is a single-center, observational, longitudinal study with an ambispective design, combining retrospective data and prospective follow-up. The study evaluates long-term clinical outcomes associated with exposure to selexipag in patients with PAH-Sch, compared with a mirror cohort of clinically similar patients who did not receive selexipag prior to its availability at the center. To reduce confounding and indication bias inherent to observational comparisons, analyses are conducted using propensity score matching.

All treatment decisions, including initiation and intensification of therapy, are made exclusively by the treating physicians as part of routine clinical care. The study does not mandate any intervention, treatment assignment, or protocol-driven management. Data are obtained from medical records and standard follow-up visits. By using real-world data and robust observational methods, this study aims to contribute clinically relevant evidence on long-term outcomes in schistosomiasis-associated pulmonary arterial hypertension.

Inclusion criteria

Adults aged 18 years or older.

• Confirmed diagnosis of pulmonary arterial hypertension associated with schistosomiasis (PAH-Sch).
• Diagnosis of pre-capillary pulmonary arterial hypertension confirmed by right heart catheterization, performed at any time prior to the index date (T0), as documented in the medical record.
• Evidence of schistosomiasis infection, including epidemiological history and ultrasonographic findings compatible with hepatosplenic schistosomiasis.
• Previous antiparasitic treatment for schistosomiasis.
• Clinical stability at the index date, defined as absence of progressive right heart failure or clinical worsening within the previous 12 weeks.
• World Health Organization (WHO) functional class I-III at the index date.
• Stable background pulmonary arterial hypertension-specific therapy with a phosphodiesterase-5 inhibitor and/or endothelin receptor antagonist for at least 12 weeks prior to the index date.
• For the treated cohort: initiation of oral selexipag as part of routine clinical care.
• For the mirror cohort: eligibility for therapeutic escalation at the index date without exposure to selexipag.

Exclusion criteria

• World Health Organization (WHO) functional class IV at the index date.
• Progressive right heart failure or clinical deterioration within the 12 weeks prior to the index date.
• Documented formal contraindication to selexipag in the medical record.
• Insufficient baseline data at the index date to allow clinical characterization or inclusion in propensity score analyses.