title: Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study.
abstract: Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH.
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson olivier.sitbon@bct.aphp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
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.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: Service de Pneumologie et d'oncologie thoracique, Hôpital Universitaire de Caen, Caen.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bergot
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: Elise Artaud
authors.initials: EA
authors.lastname: Macari
authors.affiliation: Service de Cardiologie, CHU, Grenoble.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouvaist
authors.affiliation: Service de Cardiologie, CHU Gabriel-Montpied, Clermont-Ferrand.
authors.forename: Claire
authors.initials: C
authors.lastname: Dauphin
authors.affiliation: Service de Cardiologie, Hôpital Haut-Lévêque, Pessac, France.
authors.forename: François
authors.initials: F
authors.lastname: Picard
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bulifon
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Univ. Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre APHP, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Soins Intensifs, DHU Thorax Innovation, Hôpital de Bicêtre, Le Kremlin-Bicêtre INSERM U999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D004359:Drug Therapy, Combination / Q000379:methods; D011464:Epoprostenol / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage; D011379:Prognosis; D011687:Purines / Q000008:administration & dosage; D012042:Registries; D012189:Retrospective Studies; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage; D013450:Sulfones / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D000077300:Bosentan