title: Initial dual oral combination therapy in pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France olivier.sitbon@aphp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sattler
authors.affiliation: Service de Médecine Vasculaire et Thérapeutique, Hôpital Nord, CHU, Saint-Etienne, France Univ. Jean-Monnet, Groupe de Recherche sur la Thrombose (EA 3065), INSERM, CIC1408, Saint-Etienne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bertoletti
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.affiliation: Univ. Lyon-1, Hospices Civils de Lyon, Centre de Référence des maladies pulmonaires rares, Centre de Compétences de l'Hypertension Pulmonaire, Hôpital Louis Pradel, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.affiliation: Hôpital Cardiologique de Lille, Centre de compétences de l'Hypertension Pulmonaire, Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: De Groote
authors.affiliation: CHU Nancy, Pôle des spécialités médicales, Département de Pneumologie, Vandoeuvre-lès-Nancy, France Université de Lorraine, INGRES, EA 7298, Vandoeuvre-lès-Nancy, France.
authors.forename: Ari
authors.initials: A
authors.lastname: Chaouat
authors.affiliation: CHU Rennes, Service de Cardiologie et Maladies Vasculaires, INSERM U1099, Rennes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Chabannes
authors.affiliation: Hôpital Côte de Nacre, Centre de compétences Basse Normandie de l'Hypertension Pulmonaire, Université de Caen-Basse Normandie, Caen, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bergot
authors.affiliation: Centre Hospitalier Universitaire, Service de cardiologie, Grenoble, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouvaist
authors.affiliation: CHU Clermont-Ferrand, Hôpital Gabriel Montpied, Service de cardiologie et maladies vasculaires, Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dauphin
authors.affiliation: Université de Montpellier; INSERM U1046, UMR 9214, Hôpital Arnaud de Villeneuve, Service de pneumologie, Montpellier, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
authors.affiliation: Cardiology Dept, Rouen University Health Centre, Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bauer
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Marc
authors.identifier: 0000-0003-0703-2892
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM UMR_S 999, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000077300:Bosentan; D004053:Diethylpropion; D004359:Drug Therapy, Combination; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010666:Phenylpropionates / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000068581:Tadalafil / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D010666:Phenylpropionates; D011724:Pyridazines; D013449:Sulfonamides; D000068581:Tadalafil; D000068677:Sildenafil Citrate; C467894:ambrisentan; D000077300:Bosentan; D004053:Diethylpropion