The effect of losartan on global and focal cerebral perfusion and on renal function in hypertensives in mild early ischaemic stroke.
BACKGROUND
Secondary prevention of stroke with antihypertensive drugs is now standard practice, but it is unclear how soon after a cerebrovascular event antihypertensive therapy should be initiated or re-started. Due to impaired cerebral autoregulation, changes in systemic blood pressure may be reflected in cerebral perfusion, especially in hypertensive patients immediately post-stroke. Conversely, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin II receptor antagonist (ARA) losartan on mean arterial blood pressure (MABP), global and focal cerebral blood flow (CBF), and glomerular filtration rate (GFR) in hypertensive patients 2-7 days after stroke.


METHODS
Twenty-four patients without occlusive carotid disease but with MABP between 110 and 145 mmHg were studied within 2-7 days of ischaemic stroke/transient ischaemic attack (TIA). They were randomized to receive either placebo or losartan (25 or 50 mg daily). MABP and internal carotid artery (ICA) flow were measured at baseline, over the following 24 h and at 2 weeks. Brain hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO SPECT) was performed before dosing and at the estimated time of peak drug effect (6-8 h after the first dose). GFR was measured at baseline and at 2 weeks.


RESULTS
The mean National Institutes of Health (NIH) score of randomized patients was 2.6; losartan was generally well tolerated and no patient suffered a deterioration in neurological function. A mean placebo-corrected intra-subject reduction in MABP of 9.5 mmHg was observed in treated patients from 1-12 h (P = 0.0001), with a maximal fall of 18.1 mmHg at 9 h post-dose (P = 0.002). No change occurred in ICA flow, or cortical or hemispheric CBF measured by HMPAO SPECT. No significant change in GFR was seen within or between groups.


CONCLUSIONS
Losartan may be introduced within 2-7 days of mild stroke in hypertensive patients in whom significant carotid occlusive disease has been excluded without affecting global or regional CBF, or affecting GFR.
Nazir
Fozia S
FS
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK. fsn2g@clinmed.gla.uk
Overell
James R
JR
Bolster
Alison
A
Hilditch
Tom E
TE
Reid
John L
JL
Lees
Kennedy R
KR
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects*; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*
D000959:Antihypertensive Agents; D019808:Losartan