Sildenafil for Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial

被引:82
作者
Lederer, David J. [1 ]
Bartels, Matthew N. [2 ]
Schluger, Neil W.
Brogan, Frances [3 ]
Jellen, Patricia [3 ]
Thomashow, Byron M.
Kawut, Steven M. [4 ,5 ]
机构
[1] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Coll Phys & Surg,Dept Med,Div Pulm Allergy & Crit, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Rehabil & Regenerat Med, New York, NY 10032 USA
[3] New York Presbyterian Hosp, New York, NY USA
[4] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA
[5] Univ Penn, Sch Med, Dept Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA
关键词
Sildenafil; Emphysema; Clinical Trial; COPD; Pulmonary hypertension; QUALITY-OF-LIFE; HYPERTENSION; COPD; HEMODYNAMICS; NIFEDIPINE; SYMPTOMS; THERAPY; ASTHMA;
D O I
10.3109/15412555.2011.651180
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Rationale: Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema. Methods: We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise. Results: Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005). Conclusions: Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.govNCT00104637).
引用
收藏
页码:268 / 275
页数:8
相关论文
共 22 条
[1]   Sildenafil improves hemodynamic parameters in COPD - an investigation of six patients [J].
Alp, S. ;
Skrygan, M. ;
Schmidt, W. E. ;
Bastian, A. .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 2006, 19 (06) :386-390
[2]  
[Anonymous], 1980, ANN INTERN MED, V93, P391
[3]   Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension [J].
Blanco, Isabel ;
Gimeno, Elena ;
Munoz, Phillip A. ;
Pizarro, Sandra ;
Gistau, Concepcion ;
Rodriguez-Roisin, Robert ;
Roca, Josep ;
Albert Barbera, Joan .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (03) :270-278
[4]  
FLENLEY DC, 1981, LANCET, V1, P681
[5]   Sildenafil citrate therapy for pulmonary arterial hypertension [J].
Galiè, N ;
Ghofrani, HA ;
Torbicki, A ;
Barst, RJ ;
Rubin, LJ ;
Badesch, D ;
Fleming, T ;
Parpia, T ;
Burgess, G ;
Branzi, A ;
Grimminger, F ;
Kurzyna, M ;
Simonneau, G .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2148-2157
[6]   Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial [J].
Ghofrani, HA ;
Wiedemann, R ;
Rose, F ;
Schermuly, RT ;
Olschewski, H ;
Weissmann, N ;
Gunther, A ;
Walmrath, D ;
Seeger, W ;
Grimminger, F .
LANCET, 2002, 360 (9337) :895-900
[7]   Stroke volume increase to exercise in chronic obstructive pulmonary disease is limited by increased pulmonary artery pressure [J].
Holverda, S. ;
Rietema, H. ;
Westerhof, N. ;
Marcus, J. T. ;
Gan, C. T-J ;
Postmus, P. E. ;
Vonk-Noordegraaf, A. .
HEART, 2009, 95 (02) :137-141
[8]   Acute effects of sildenafil on exercise pulmonary hemodynamics and capacity in patients with COPD [J].
Holverda, Sebastlaan ;
Rietema, Heleen ;
Bogaard, Harm J. ;
Westerhof, Nico ;
Postmus, Pieter E. ;
Boonstra, Anco ;
Vonk-Noordegraaf, Anton .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 2008, 21 (03) :558-564
[9]   QUALITY-OF-LIFE, SYMPTOMS AND PULMONARY-FUNCTION IN ASTHMA - LONG-TERM TREATMENT WITH NEDOCROMIL SODIUM EXAMINED IN A CONTROLLED MULTICENTER TRIAL [J].
JONES, PW .
EUROPEAN RESPIRATORY JOURNAL, 1994, 7 (01) :55-62
[10]   EFFECT OF NIFEDIPINE ON PHYSIOLOGICAL SHUNTING AND OXYGENATION IN CHRONIC OBSTRUCTIVE PULMONARY-DISEASE [J].
KALRA, L ;
BONE, MF .
AMERICAN JOURNAL OF MEDICINE, 1993, 94 (04) :419-423