Patrizio Vitulo1, Anna Stanziola2, Marco Confalonieri3, Daniela Libertucci4, Tiberio Oggionni5, Paola Rottoli6, Giuseppe Paciocco7, Fabio Tuzzolino8, Lavinia Martino1, Marta Beretta1, Adriana Callari1, Andrea Amaducci1, Roberto Badagliacca9, Roberto Poscia9, Federica Meloni5, Rosa Metella Refini6, Pietro Geri3, Sergio Baldi4, Stefano Ghio10, Michele D'Alto11, Paola Argiento11, Matteo Sofia2, Mara Guardamagna12, Beatrice Pezzuto9, Carmine Dario Vizza13. 1. 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. 2. I Respiratory Disease Clinic, Department Of Clinical Medicine and Surgery, Federico II University, Naples, Italy. 3. Department of Pneumology and Respiratory Intermediate Care Unit, University Hospital of Cattinara, Trieste, Italy. 4. Division of Pneumology, Department of Internal Medicine, Città Della Salute e Della Scienza, Turin, Italy. 5. Pulmonology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy. 6. Department of Medical and Surgical Sciences & Neurosciences, University of Siena, Siena, Italy. 7. Pulmonary Clinic Unit, San Gerardo Hospital, University of Milano Bicocca, Monza, Italy. 8. Office of Research, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per I Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy. 9. Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy. 10. Centro Studi AIPO, Italian Association of Hospital Pneumologists, Milan, Italy. 11. Department of Cardiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy. 12. Department of Cardiology, Second University of Naples, Monaldi Hospital, Naples, Italy. 13. Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Disease, Sapienza University of Rome, Italy. Electronic address: dario.vizza@uniroma1.it.
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.
RCT Entities:
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: Kirsten E Coffman; Timothy B Curry; Niki M Dietz; Steven C Chase; Alex R Carlson; Briana L Ziegler; Bruce D Johnson Journal: Physiol Rep Date: 2018-01