Current epoprostenol use in patients with severe idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension: Data from the French pulmonary hypertension registry
Introduction
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance, leading to right heart failure and death. Without specific treatment, idiopathic, heritable and anorexigen-associated PAH (IHA-PAH) is associated with a 2.8-year median survival time after diagnosis [1].
Over the last two decades, new therapeutic agents have considerably improved the clinical status and prognosis of PAH patients. Three classes of drugs, each affecting different mechanisms involved in the pathogenesis of PAH, are currently available for the management of PAH [2]. Endothelin receptor antagonists (ERAs) and phosphodiesterase type-5 (PDE-5) inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous (i.v.) or subcutaneous infusion, or nebulization. However, PAH continues to cause substantial morbidity and mortality [3].
Epoprostenol, a synthetic analog of prostacyclin, was the first therapy approved by the FDA for the treatment of PAH (1995). Two prospective studies initially showed sustained clinical benefit on hemodynamics and exercise capacity with i.v. epoprostenol compared with conventional therapy for idiopathic PAH (IPAH) patients [4], [5]. In the 12-week study by Barst et al., epoprostenol significantly improved short-term survival compared with conventional therapy [5]. The positive impact of epoprostenol on long-term survival in IPAH has subsequently been described in several single center, observational, uncontrolled trials [6], [7], [8], [9].
Recent evidence-based guidelines recommend i.v. epoprostenol for the long-term treatment of PAH in patients with New York Heart Association (NYHA) functional classes III and IV and in patients who failed to respond to oral or inhaled treatment [10], [11]. Combinations with other PAH medications is possible [2], but limited data have been published on epoprostenol therapy since the advent of oral treatments.
In this study, we describe the use of epoprostenol in the management of patients with IHA-PAH. The effect of epoprostenol treatment administered as first-line or add-on therapy on clinical and hemodynamic status, as well as on survival was investigated in a cohort of consecutive patients enrolled in the French pulmonary hypertension (PH) registry.
Section snippets
Study design
This observational study evaluated all incident i.e. newly diagnosed (≤ 1 year), consecutive patients with IHA-PAH who were enrolled in the French PH registry between 2006 and 2010 and treated with i.v. epoprostenol. The French PH registry was initiated in 26 French reference centers and enrolled consecutive patients with PH. IHA-PAH patients were characterized as nontreatment-naïve for those who had received PAH-specific therapy after enrolment and before epoprostenol initiation and
Study population
The study evaluated 209 adult patients enrolled in the French PH registry who were newly diagnosed (≤ 1 year) with PH and treated with i.v. epoprostenol. Most patients on epoprostenol were in PH group 1, and had IHA-PAH or PAH associated with connective tissue disease (Fig. 1). The current analysis focused on the 78 IHA-PAH patients. IHA-PAH patients were further characterized as nontreatment-naïve (n = 35) for those who had received PAH-specific therapy after enrolment and before epoprostenol
Discussion
The present study describes the use of epoprostenol in the current management of patients with severe IHA-PAH enrolled in the French PH registry. With the availability of novel disease-specific therapies, treatment options for PAH patients have significantly broadened since the era when epoprostenol was the only approved PAH treatment. In the historical cohorts described by Sitbon et al. [9] and Mclaughlin et al. [8], patients exclusively received epoprostenol. In the present study, in line
Funding
This is an academic registry and was supported in part by Actelion Pharmaceuticals Ltd., which funded statistical analysis and editorial assistance.
Conflicts of interest
Emmanuel Bergot has received payment for board membership from Actelion and Eli Lilly, for lectures from Actelion, Eli Lilly, and Pfizer, and for travel/meeting expenses from Actelion, Eli Lilly, GlaxoSmithKline, and Pfizer.
Olivier Sitbon has received payment for consultancy and lectures from Actelion, Bayer HealthCare, Eli Lilly, GlaxoSmithKline, Pfizer, and United Therapeutics, and for the development of educational presentations from Actelion, Eli Lilly, and Pfizer. His institution has
Acknowledgments
The authors thank Jean-Christophe Lemarié for the statistical analyses (Effi-Stat, Paris, France) and Sylvie I. Ertel (Sundgau Medical Writers, Habsheim, France) for the editorial assistance.
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All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.