Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.
OBJECTIVE
To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments.


METHODS
A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial.


METHODS
Five hospitals in England.


METHODS
Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm).


METHODS
Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm.


METHODS
The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death.


RESULTS
180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy.


CONCLUSIONS
Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.
Potter
J
J
University of East Anglia, UK.
Mistri
A
A
Brodie
F
F
Chernova
J
J
Wilson
E
E
Jagger
C
C
James
M
M
Ford
G
G
Robinson
T
T
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000191:economics / Q000494:pharmacology* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003680:Deglutition Disorders / Q000188:drug therapy / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006761:Hospitals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D007741:Labetalol / Q000191:economics / Q000494:pharmacology* / Q000627:therapeutic use*; D017706:Lisinopril / Q000191:economics / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000191:economics / Q000494:pharmacology* / Q000627:therapeutic use*; D010919:Placebos; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D010919:Placebos; D010656:Phenylephrine; D017706:Lisinopril; D007741:Labetalol