high blood pressure occurs in around 80% of patients with acute ischemic stroke   and usually decreases over the following 7 days .   whether this elevated blood pressure is a physiological and protective reaction or a side effect of a generalised stress reaction that is in fact harmful to the newly damaged brain and whether it should be lowered or not is yet to be answered .
american ( aha ) and european ( eso ) guidelines recommend not to treat elevated blood pressure unless above 220/120  mmhg and describe an urgent need for large well - designed trials to address this issue [ 4 , 5 ] .
currently there are two large ongoing trials : the  efficacy of nitric oxide in stroke  trial ( enos ) compares nitric oxide versus placebo and continuing versus stopping previously taken antihypertensive agents in acute stroke .
enchanted compares low dose versus normal dose of recombinant tissue - type plasminogen activator ( r - tpa ) and intensive blood pressure reduction versus standard reduction in thrombolysed patients .  
this article focuses on currently available data , the contraries of the results , and potential solutions .
a post hoc analysis of the international stroke trial found a u - shaped relationship between initial blood pressure and outcome , indicating that systolic blood pressure of around 140180  mmhg is associated with best outcome .
these findings were confirmed in another study showing that very high and very low initial blood pressure is associated with increased death rates .
high blood pressure was also independently associated with recurrent ischemic stroke and cerebral edema [ 1 , 9 ] .
patients with very low initial blood pressure had a higher incidence of heart failure and coronary heart disease .
high blood pressure after acute ischemic stroke causes brain edema , and brain edema decreases cerebral blood flow [ 11 , 12 ] , thus aggravating cerebral ischemia .
another mechanism could be that endogenous tpa release is reduced when blood pressure is high due to the damage at the endothelium [ 1315 ] .
one critique of those studies is that blood pressure was measured only on admission , usually several hours after stroke onset [ 1 , 8 , 16 , 17 ] .
however , variability and duration of high blood pressure in the first hours after stroke onset may be more relevant for prognosis .
several observational studies looked into the prognosis of spontaneous change in blood pressure during the acute phase with divergent results .
the barcelona downtown stroke registry found that early decrease of systolic blood pressure by 2030% was associated with full recovery ( or 2.9 , 95% ci 1.36.3 ) . a decrease in systolic blood pressure within 12 hours
spontaneous decrease of blood pressure within 24 hours was associated with poor outcome   and early neurological deterioration
.   there might be a bias when looking into spontaneous decrease of blood pressure and correlating it to outcome .
rapid spontaneous decrease might reflect less severe stroke , recanalization of the vessel , or might be due to cardiac insufficiency , all of which have an independent effect on outcome . so it might be a sign for a rapidly resolving or rapidly deteriorating process , explaining the divergent results .
several randomised controlled trials addressed the topic of blood pressure management in acute stroke ( see table 1 ) .
the trials are heterogeneous regarding time to treatment , degree and speed of effective blood pressure reduction , substances used , and the stroke subgroups included ( i.e. , ischemic , hemorrhagic strokes , or both ) .  

beta - blockers given within 48 hours after hemispheric stroke increased mortality ( best ) .
the treatment groups , however , were unbalanced with more severely disabled patients in the group receiving beta blockers .
also patients did not have to have elevated blood pressure to be included in the trial .
a metaanalysis of nine trials showed a significant benefit from oral nimodipine versus placebo when given within 12 hours of symptom onset .
in contrast , intravenous nimodipine given as 1  mg / h and 2  mg / h increased the rate of poor neurological and functional outcome in ischemic stroke patients compared to placebo ( inwest ) .
a correlation was found between the amount of diastolic blood pressure reduction in the high - dose group and poor functional outcome .   intravenous magnesium administered within 12 hours lowered systolic blood pressure by 4  mmhg and showed a trend towards improved outcome in all stroke patients ( odds ratio : 0.95 , 95% ci 0.801.13 , p = 0.59 ) .
for the subgroup of patients with elevated blood pressure ( mean arterial pressure > 108  mmhg ) , improvement was significant ( odds ratio of 0.78 , 95% ci 0.610.99 ) .   smaller trials with glyceryl trinitrate showed no significant difference in functional outcome [ 26 , 27 ] but were also not powered to do so .
the early administration of labetalol and lisinopril lead to a significant reduction in blood pressure as compared to the placebo group ( mean systolic difference 10  mmhg , 95% ci 317 , p = 0.004 ) ( chhips ) . death and dependency at 3 months did not differ , but 3 months mortality was halved in the treatment group to 9,7% from 20,3% ( hr 0.4 , 95% ci 0.21.0 , p = 0.05 ) .
the cossacs trial looked into the question whether previously taken antihypertensive agents should be stopped or continued in patients with acute stroke .
the medication reduced blood pressure significantly ( 13/8  mmhg lower at two weeks ) .
no difference was seen in the primary outcome death or dependency at two weeks , but there was a significant functional improvement in the subgroup of patients with confirmed acute ischemic stroke ( relative risk 0.70 , 95% ci 0.510.99 , p = 0.045 ) .
another trial ( scast ) compared candesartan to placebo within 30 hours after onset looking at a combined vascular endpoint .
blood pressure reduction was only moderate , and no significant differences in the endpoints were seen .
a trend favouring placebo was noticed . a metaregression on actively lowered blood pressure in acute stroke including 9008 patients from randomized trials showed the lowest odds ratio ( 0.95 , 95% ci 0.111.72 ) for death or dependency with a decrease of systolic blood pressure by 14  mmhg .  
two cochrane analyses concluded that there is insufficient evidence to evaluate the effect of blood pressure changes on outcome after acute stroke [ 32 , 33 ] .
the management of blood pressure in acute ischemic stroke remains unclear due to divergent results of the studies .
the effect might be dependent on level of initial blood pressure , time to treatment , stroke severity , and history of hypertension , as well as intensity of blood pressure lowering , substances used , and administration form ( e.g. , i.v . or oral ) .
it is evident that lowering blood pressure of normotensive patients in acute stroke may lead to hypotensive events , thus deteriorating outcome .
the negative effect of the best trial might partly be explained by inclusion of normotensive patients with systolic blood pressure > 100  mmhg . in a subgroup of images
only those patients with higher blood pressure levels had a benefit ( mean arterial pressure > 108  mmhg ) .
this matches with chhips and cossacs in which mean systolic level was high ( 181  mmhg and 150  mmhg ) , and decreased mortality and improved functional outcome in the subgroup with ischemic stroke were seen , respectively [ 28 , 29 ] .
observational data showed that low initial blood pressure increased poor outcome [ 1 , 8 ] .
however , there are also trials in which treating elevated blood pressure did harm ( inwest ) or showed a trend favoring placebo ( scast ) [ 23 , 30 ] .  
significant benefit from oral nimodipine versus placebo was seen when given within 12 hours after onset , no benefit between 12 and 24 hours , and worse outcome when initiated after 24 hours . in images
, magnesium was given early at a mean of about 7 hours after onset ( max .
12 hours ) and showed a benefit in those with elevated blood pressure . in scast , treatment was started after about 17 hours and did no benefit .
in fact , the later treatment was started , the more did candesartan seem to harm the patient regarding the composite vascular endpoint . other trials showed the opposite .
nimodipine was started early ( 11 hours after onset ) and had a negative effect .
chhips and cossacs started treatment late and were neutral , even with some positive secondary endpoints [ 28 , 29 ] .
although the start of treatment is known for most of the trials , the lag until achieving effective blood pressure reduction is not .
it is agreed that a rapid and large decrease in blood pressure is dangerous for acute stroke patients .
this opinion is largely based on the data from inwest and some observational data [ 19 , 20 , 23 ] .
high - dose ( but not low - dose ) intravenous nimodipine was associated with death and dependency when diastolic blood pressure was lowered by > 20% within the first two days .
a secondary analysis of scast showed that a large systolic decrease of > 28  mmhg was significantly associated with poor outcome .
magnesium reduced blood pressure within 24 hours by 4/3  mmhg and showed a benefit for those with higher blood pressure . in chhips
the systolic blood pressure difference was 10  mmhg within the first 24 hours , and mortality was halved after 3 months .
a decrease of even 16  mmhg was achieved within 4 hours with labetalol compared to placebo , and this was found to be safe .
so the rapid reduction does not seem to be dangerous , as long as reduction is moderate .  
some trials included various classes [ 28 , 29 ] , and others looked into the effect of a single one .
the calcium channel blocker nimodipine had a positive effect when given orally within 12 hours , but a negative effect when given intravenously .
the angiotensin - converting - enzyme inhibitor lisinopril had a positive effect on 3 months mortality , and the angiotensin receptor antagonist candesartan possibly has an injurious effect on the brain .
nitric oxide donors found stable cerebral blood flow albeit reducing blood pressure effectively [ 27 , 36 ] , and the mixed alpha / beta - receptor antagonist labetalol showed reduction of 3-month mortality .
several data showed that lowering blood pressure in acute ischemic stroke is safe in terms of early neurological deterioration and functional outcome [ 2629 ] , even in the presence of carotid artery stenosis   and that it does not decrease perfusion in the region of the infarct [ 27 , 36 , 3840 ] .
trials looking at the effect of blood pressure reduction in the acute phase of stroke are heterogeneous in design , classes of antihypertensive agents , achieved blood pressure reduction , and influence on outcome . although the guideline recommendation is not to lower blood pressure in the range up to 220/120  mmhg , there might be some neuroprotective effect of very early ( first 710 hours after stroke ) and rather moderate ( 1020  mmhg ) blood pressure lowering .
substance classes may differ in that respect , but care should be taken with intravenous calcium channel blockers and angiotensin receptor antagonists . adequately powered , randomized trials , however , are urgently warranted to substantiate those speculations .
 high blood pressure is common in acute stroke patients . very high as well as 
 very low blood pressure is associated with poor outcome . 
 spontaneous fall of blood pressure within the first few days after stroke was associated both with neurological improvement and impairment . 
 several randomized trials investigated the pharmacological reduction of blood pressure versus control . 
 most trials showed no significant difference in their primary outcome apart from the inwest trial which found an increase of poor outcome when giving intravenous nimodipine . 
 nevertheless , useful information can be extracted from the published data to help guide the clinician 's decision . 
 blood pressure should only be lowered when it is clearly elevated , and early after onset , reduction should be moderate but may be achieved rapidly . 
 no clear recommendations can be given on the substances to use ; however , care should be taken with intravenous calcium channel blockers and angiotensin receptor antagonists . 
 two ongoing randomized trials will help to solve the questions on blood pressure management in acute stroke . 
1. Introduction
2. Initial Blood Pressure and Outcome
3. Spontaneous Change in Blood Pressure and Outcome
4. Intervention of Elevated Blood Pressure and Outcome
5. Discussion
6. Conclusion