Pilot study of losartan for pulmonary hypertension in chronic obstructive pulmonary disease

Background: Morbidity in COPD results from a combination of factors including hypoxia-induced pulmonary hypertension, in part due to pulmonary vascular remodelling. Animal studies suggest a role of angiotensin II and acute studies in man concur. Whether chronic angiotensin- II blockade is beneficial is unknown. We studied the effects of an angiotensin- II antagonist losartan, on haemodynamic variables, exercise capacity and symptoms. Methods: This was a double-blind, randomized, parallel group, placebo- controlled study of 48 weeks duration. Forty patients with COPD and pulmonary hypertension ( Tran tricuspid pressure gradient ( TTPG) = 30 mmHg) were randomised to losartan 50 mg or placebo. Changes in TTPG were assessed at 3, 6 and 12 months. Results: There was a trend for TTPG to increase in the placebo group ( baseline 43.4 versus 48.4 mmHg at endpoint) and stay constant in the losartan group ( baseline 42.8 versus 43.6 mmHg). More patients in the losartan group (50%) than in the placebo group (22%) showed a clinically meaningful reduction in TTPG at any timepoint; these effects seemed more marked in patients with higher baseline TTPG. There were no clear improvements in exercise capacity or symptoms. Conclusion: In this 12-month pilot study, losartan 50 mg had no statistically significant beneficial effect on TTPG, exercise capacity or symptoms in pulmonary hypertension secondary to obstructive disease. A sub-group of patients with higher TTPG may benefit.