Presented by Dr CHU Po Ngai Alvin, ICU, PYNEH, Hong Kong, on 2 June 2009
John F Potter FRCP a , Thompson G Robinson FRCP b, Gary A Ford FRCP d, Amit Mistri MRCP b, Martin James FRCP e, Julia Chernova MSc f, Carol Jagger PhD c ‡The Lancet Neurology, Volume 8, Issue 1, Pages 48 - 56, January 2009
Editor's note: This negative study is underpowered due to difficulty in recruitment, despite the fact that in the calculation for study power and the number of subjects required the assumed difference was already quite large and 1-beta was only 0.8. Results are therefore difficult to comment or apply.

Background: Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.

Methods: Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.

Findings: 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5—16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1·03, 95% CI 0·80—1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33—4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17—25] mm Hg vs 11 [5—17] mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69—1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio [HR] 0·40, 95% CI 0·2—1·0; p=0·05).

Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.
UK National Health Service Research and Development Health Technology Assessment Programme.