In patients with severe pulmonary arterial hypertension (PAH), the safety and tolerability of treatment with intravenous epoprostenol sodium containing the excipients arginine and sucrose (epoprostenol AS) were comparable to those with prior prostacyclin formulations and feasible for most individuals, according to a study published in Respiratory Research.
Researchers conducted the 6-month, prospective, open-label, observational, noninterventional study to expand clinical experience with epoprostenol AS—a thermostable epoprostenol formulation—particularly with respect to safety, tolerability, and patient survival.
Fifteen patients with PAH invasively diagnosed by right heart catheterization (mean pulmonary arterial pressure [mPAP], ≥25 mmHg at rest; pulmonary arterial wedge pressure, ≤15 mmHg) categorized as World Health Organization (WHO) functional class III (n=10) or IV (n=5) were consecutively included in the study between March 2018 and August 2020. The last participant completed treatment in March 2021.
All of the patients received at least dual oral combination therapy with phosphodiesterase-5 inhibitors and endothelin-receptor antagonists, and they all required treatment escalation. The eligible patients either reported an unsatisfying long-term clinical response or were still in an intermediate- or high-risk group despite receiving dual combination therapy.
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The mean patient age was 60±13.7 years. Overall, 12 participants were female and 3 participants were male. The mPAP of the participants was 54.8±8.9 mmHg, and the mean pulmonary vascular resistance was 4.4±0.7 Wood units. The majority of participants had been diagnosed with idiopathic PAH or PAH associated with connective tissue disease.
All clinical data were evaluated at baseline, after 3 months, and after 6 months. All adverse events (AEs) and serious adverse events (SAEs) were reported. Survival from epoprostenol AS initiation was assessed at the last patient out.
Patients were treated with a mean dosage of epoprostenol AS of 7.9±3.9 ng/kg/min (median, 7.9±3.9 ng/kg/min). Of the 15 participants, 11 patients completed the study, with 1 withdrawal and 3 deaths reported. After a mean follow-up of 19.1±13.5 months (median, 18.0 months), 7 participants died and 3 were listed for lung transplantation.
Seven AEs (nausea [n=3], flushing [n=2], diarrhea [n=1], headache [n=1]) and 3 SAEs (catheter infection [n=2], catheter occlusion [n=1]) were reported to be related to treatment with epoprostenol AS. The 1-year and 2-year survival rates were 73.3% and 52.4%, respectively.
The authors concluded, “In future applications/trials the up-titration process should be pushing for higher dosages of epoprostenol in the occurrence of side effects, as the achievement of a high and effective dosage is crucial for the clinical benefit of the patients.”
Degering J, Egenlauf B, Harutyunova S, et al. Tolerability, safety and survival in patients with severe pulmonary arterial hypertension treated with intravenous epoprostenol (Veletri®): a prospective, 6-months, open label, observational, non-interventional study. Respir Res. 2023;24(1):18. doi:10.1186/s12931-022-02296-z