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.


CONCLUSIONS
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.
Morrell
Nicholas W
NW
Department of Respiratory Medicine, Imperial College School of Medicine, London, UK. nwm23@cam.ac.uk
Higham
Matthew A
MA
Phillips
Peter G
PG
Shakur
B Haleema
BH
Robinson
Paul J
PJ
Beddoes
Ray J
RJ
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D011788:Quality of Life; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D019808:Losartan