Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial

• Published in: The Journal of heart and lung transplantation Vol. 36; no. 2; pp. 166 - 174
• Main Authors: Vitulo, Patrizio, Stanziola, Anna, Confalonieri, Marco, Libertucci, Daniela, Oggionni, Tiberio, Rottoli, Paola, Paciocco, Giuseppe, Tuzzolino, Fabio, Martino, Lavinia, Beretta, Marta, Callari, Adriana, Amaducci, Andrea, Badagliacca, Roberto, Poscia, Roberto, Meloni, Federica, Refini, Rosa Metella, Geri, Pietro, Baldi, Sergio, Ghio, Stefano, D’Alto, Michele, Argiento, Paola, Sofia, Matteo, Guardamagna, Mara, Pezzuto, Beatrice, Vizza, Carmine Dario
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2017
• Subjects: Adult; Aged; Aged, 80 and over; BODE index; chronic obstructive pulmonary disease; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; end-stage lung disease; Female; Follow-Up Studies; Hemodynamics - drug effects; Humans; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - drug therapy; lung transplantation; Male; Middle Aged; Patient Selection; Pilot Projects; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Gas Exchange - drug effects; pulmonary hypertension; Reference Values; Risk Assessment; Severity of Illness Index; sildenafil; Sildenafil Citrate - administration & dosage; Treatment Outcome; Vascular Resistance - drug effects; end-stage lung disease; BODE index; lung transplantation; sildenafil; pulmonary hypertension; chronic obstructive pulmonary disease
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2016.04.010

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. 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. 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. 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.