Treatment with inhaled Ventavis (iloprost) has limited effectiveness in improving the survival rate of patients with pulmonary arterial hypertension (PAH), despite the clinical improvements it induces, real-world data suggests.
These findings resulted from an analysis of data collected in the observational Spanish REHAP registry. They were recently reported in the study, “Real-life experience of inhaled iloprost for patients with pulmonary arterial hypertension: Insights from the Spanish REHAP registry,” published in the International Journal of Cardiology.
Ventavis, an approved therapy marketed by Actelion, was designed to mimic the effects of the natural vasodilator prostacyclin. Administered by inhalation, this synthetic compound has been shown to have advantages over other prostacyclin-based treatment formulations.
In clinical trials, Ventavis demonstrated a good safety profile and the capability to provide long-term benefits — for up to five years — in patients with moderate to severe PAH (WHO functional classification III and IV) when used alone or in combination with other approved therapies.
Spanish researchers have now analyzed real-world clinical data to gain better insight into the therapeutic effectiveness of inhaled Ventavis in PAH patients. They used data from 267 PAH patients, at least 14 years of age (median age of 54 years), who were enrolled in the voluntary, observational Spanish REHAP registry between 1998 and 2016, and who had received inhaled Ventavis as a first-line or sequential therapy.
The median time between PAH diagnosis and the start of Ventavis treatment was eight months, with 61% of the patients falling into WHO functional classification III. In 87 cases, Ventavis was the first PAH treatment, with 60 patients using it alone and 27 in combination with other therapies such as phosphodiesterase 5 inhibitors (PDE-5i).
Follow-up data at one year was available for 157 PAH patients, of whom 120 continued the initial treatment with inhaled Ventavis. At 12 months, 63 patients (24% of the initial analyzed population) had died, and four (2%) had undergone lung transplants.
Comparison of clinical parameters before and after one year of treatment revealed significant improvements in WHO functional classification, but without clear benefits in the physical capacity of patients.
Three years after the start of Ventavis treatment, 99 (30%) patients had died, and 10 (4%) had undergone lung transplants. At this time, significant improvements in both WHO functional classification and physical capacity were reported for those who continued the treatment.
Collectively, the data revealed that cumulative transplant-free survival rates from the beginning of Ventavis treatment were 74% at one year and 54% at three years. Survival rates upon stopping the treatment were 52% at one year and 25% at three years, “which reflects the deleterious effect of treatment discontinuation,” according to the researchers.
These survival rates were not affected by different treatment regimens, which were very similar between patients who had received Ventavis alone or in combination with other therapies.
Ventavis was not found to prevent long-term symptom worsening in patients who had a higher risk of a poorer outcome — namely, older patients who had more severe PAH and worse physical performance. Transplant-free survival rates in this population were 52% at one year and 34% at three years, compared with 85% at one year and 63% at three years in the PAH population with a low risk of symptom worsening.
“Our results show that inh-ILO [inhaled Ventavis] — the most frequently used prostanoid in Spain —, has low effectiveness in patients receiving it as first-line therapy, […] with a 3-year survival rate of 53% despite significant physical and functional performance,” the researchers wrote.
The team believes this could in part be due to the use of Ventavis in patients with severe PAH, and also the high rate of treatment withdrawal (up to 75%). “Adequate use of the different prostanoids according to severity of patients may help to overcome the underuse of prostanoids,” the researchers suggested.