Longitudinal Outcomes of Patients With Group 3 Pulmonary Hypertension Treated With Iloprost

Group 3 pulmonary hypertension (PH), associated with chronic lung diseases such as interstitial lung disease, represents a common and clinically challenging PH phenotype, frequently associated with reduced exercise capacity, increased oxygen requirements, and higher mortality. Unlike pulmonary arterial hypertension (Group 1), where targeted therapies have demonstrated clear benefits, treatment options for Group 3 PH remain limited and are primarily focused on management of the underlying lung disease and supportive measures.

The use of systemic pulmonary vasodilators in this population is controversial due to the potential risk of worsening ventilation-perfusion mismatch and hypoxemia. Inhaled prostacyclin analogues may offer a more selective therapeutic approach by preferentially targeting well-ventilated lung regions, potentially mitigating these risks. Inhaled iloprost, approved for pulmonary arterial hypertension, has been used off-label in selected patients with Group 3 PH; however, available evidence is limited and largely derived from small or short-term studies. Data describing real-world patient profiles, treatment patterns, and longitudinal clinical outcomes remain scarce.

Risk stratification has become a key component of disease monitoring in pulmonary hypertension. The COMPERA 2.0 model, which incorporates clinical and non-invasive parameters into a four-stratum risk framework, has demonstrated sensitivity to detect prognostically meaningful changes over time.

This retrospective observational study aims to characterize the clinical evolution of patients with Group 3 PH treated with inhaled iloprost in routine practice. The primary focus is the longitudinal change in risk status according to the COMPERA 2.0 four-stratum model. In addition, the study will explore changes in functional parameters such as WHO functional class and six-minute walk distance, biomarker trends when available, patterns of iloprost use (including monotherapy or combination therapy), and the occurrence of relevant clinical events such as hospitalizations, treatment escalation, and treatment discontinuation.

Data will be obtained from existing medical records of patients followed in a specialized pulmonary hypertension center, without additional patient contact or intervention.

Inclusion criteria

• Age ≥18 years
• Diagnosis of group 3 pulmonary hypertension confirmed by right heart catheterization, defined as mean pulmonary artery pressure >20 mmHg, pulmonary artery wedge pressure ≤15 mmHg, and pulmonary vascular resistance >2 Wood units
• Presence of documented underlying chronic lung disease (e.g., interstitial lung disease confirmed by high-resolution computed tomography with restrictive pattern on pulmonary function testing, or chronic obstructive pulmonary disease)
• Use of inhaled iloprost for a minimum of 3 months, documented in medical records
• Availability of baseline clinical data (at initiation of inhaled iloprost) and at least one follow-up assessment

Exclusion criteria

• Pulmonary hypertension from other clinical groups (Groups 1, 2, 4, or 5) as the predominant diagnosis
• Insufficient clinical information in medical records to allow characterization or longitudinal assessment