title: Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD.
  
  
  METHODS
  After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter.
  
  
  RESULTS
  The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups.
  
  
  CONCLUSIONS
  This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Vitulo
authors.affiliation: I Respiratory Disease Clinic, Department Of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Stanziola
authors.affiliation: Department of Pneumology and Respiratory Intermediate Care Unit, University Hospital of Cattinara, Trieste, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Confalonieri
authors.affiliation: Division of Pneumology, Department of Internal Medicine, Città Della Salute e Della Scienza, Turin, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Libertucci
authors.affiliation: Pulmonology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Tiberio
authors.initials: T
authors.lastname: Oggionni
authors.affiliation: Department of Medical and Surgical Sciences & Neurosciences, University of Siena, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rottoli
authors.affiliation: Pulmonary Clinic Unit, San Gerardo Hospital, University of Milano Bicocca, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paciocco
authors.affiliation: Office of Research, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per I Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Tuzzolino
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Martino
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Beretta
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Callari
authors.affiliation: Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Amaducci
authors.affiliation: Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Badagliacca
authors.affiliation: Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Poscia
authors.affiliation: Pulmonology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Meloni
authors.affiliation: Department of Medical and Surgical Sciences & Neurosciences, University of Siena, Siena, Italy.
authors.forename: Rosa Metella
authors.initials: RM
authors.lastname: Refini
authors.affiliation: Department of Pneumology and Respiratory Intermediate Care Unit, University Hospital of Cattinara, Trieste, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Geri
authors.affiliation: Division of Pneumology, Department of Internal Medicine, Città Della Salute e Della Scienza, Turin, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Baldi
authors.affiliation: Centro Studi AIPO, Italian Association of Hospital Pneumologists, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ghio
authors.affiliation: Department of Cardiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: D'Alto
authors.affiliation: Department of Cardiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Argiento
authors.affiliation: I Respiratory Disease Clinic, Department Of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Sofia
authors.affiliation: Department of Cardiology, Second University of Naples, Monaldi Hospital, Naples, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Guardamagna
authors.affiliation: Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pezzuto
authors.affiliation: Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy. Electronic address: dario.vizza@uniroma1.it.
authors.forename: Carmine Dario
authors.initials: CD
authors.lastname: Vizza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D000068677:Sildenafil Citrate
keywords: BODE index; chronic obstructive pulmonary disease; end-stage lung disease; lung transplantation; pulmonary hypertension; sildenafil