Controlling Hypertension and Hypotension Immediately Post-Stroke Trial "CHHIPS"

Completed

Phase N/A Results

Results

Greater BP reductions were seen from 4 to 24 hours following administration with lisinopril (oral or sublingual) or labetalol (oral or intravenous) in dysphagic and non-dysphagic acute stroke patients compared to placebo. SBP, but not DBP, differences between active treatment and placebo were maintained up to two weeks. Discontinuation of medication were similar in active and placebo groups, though greater in dysphagic and non-dysphagic subjects. No increase in adverse side effects was seen with active treatment. BP reduction was not associated with deterioration in neurological status at 72 hours. Active treatment did not alter death or disability at 2 weeks. Borderline reductions in 90 day mortality with active treatment but small number of events. The CHHIPS pilot data emphasise the need for a full scale trial to see if these encouraging preliminary results can be reproduced. 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).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.