Initial dual oral combination therapy in pulmonary arterial hypertension

Olivier Sitbon (1, 2, 3) , Caroline Sattler (1, 2, 3) , Laurent Bertoletti (4, 5) , Laurent Savale (1, 2, 3) , Vincent Cottin (6, 7) , Xavier Jaïs (1, 2, 3) , Pascal de Groote , Ari Chaouat (8, 9) , Céline Chabannes (10) , Emmanuel Bergot (11) , Helene Bouvaist (12) , Claire Dauphin (13) , Arnaud Bourdin (14, 15) , Fabrice Bauer (16) , David Montani (1, 3, 2) , Marc Humbert (1, 3, 2) , Gérald Simonneau (1, 3, 2)

1 DHU TORINO - Service de Pneumologie et Réanimation Respiratoire
2 UP11 - Université Paris-Sud - Paris 11
3 Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
4 CIC-EC - Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne
5 GRT - Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque
6 UCBL - Université Claude Bernard Lyon 1
7 Service de Pneumologie
8 Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
9 INGRES - Interactions Gènes-Risques environnementaux et Effets sur la Santé
10 LTSI - Laboratoire Traitement du Signal et de l'Image
11 Service de pneumologie [CHU Caen]
12 Service de Cardiologie
13 CHU Gabriel Montpied [Clermont-Ferrand]
14 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
15 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
16 Service de cardiologie [CHU Rouen]

Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met. This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III−IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8). All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively. Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment.

Domains: Life Sciences [q-bio]; Human health and pathology; Pulmonology and respiratory tract; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology

Olivier Sitbon, Caroline Sattler, Laurent Bertoletti, Laurent Savale, Vincent Cottin, et al.. Initial dual oral combination therapy in pulmonary arterial hypertension. European Respiratory Journal, 2016, 47 (6), pp.1727-1736. ⟨10.1183/13993003.02043-2015⟩. ⟨hal-01301539⟩