Sildenafil is a phosphodiesterase-5 inhibitor that has been approved for the treatment of pulmonary arterial hypertension with orphan drug designation. Sildenafil modulates the nitric oxide (NO) pathway in the vessel wall. Since this pathway is impaired in pulmonary arteries of patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD), the investigators hypothesized that sildenafil might improve pulmonary hemodynamics and increase exercise tolerance in this condition.

It is a prospective, randomized, double-blind, placebo controlled trial to assess the effect of 3 months treatment with sildenafil (20 mg/8 h), added to a pulmonary rehabilitation program, on exercise tolerance. Subjects: 60 patients (30 by treatment group). Main end-point variable: endurance time in constant work exercise test (CWET). Other measurements: 6 min walk distance, performance in incremental exercise test, physiological and metabolic response at iso-time and iso-load in CWET, dyspnea, and health-related quality of life.

Inclusion Criteria:

• COPD, FEV1 < 80% ref. and FEV1/FVC < 0.7 post bronchodilator
• Age 40-80 years
• Pulmonary hypertension
• Consent to participate in the study

Exclusion Criteria:

• Pulmonary or extrapulmonary disease that modifies gas exchange or pulmonary hemodynamics
• Recent exacerbation (<4 weeks) (temporally)
• Patients treated with nitrates or CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir)
• Ischemic optic neuropathy
• Patients treated with phosphodiesterase-5 inhibitors
• Patients with ischemic cardiopathy
• Systemic disease that could modified the results
• Patients unable to practise exercise