You are on page 1of 7

Topical Reviews

Section Editors: Marc Fisher, MD, and Kennedy Lees, MD

Management of Blood Pressure for Acute and


Recurrent Stroke
Venkatesh Aiyagari, MBBS, DM; Philip B. Gorelick, MD, MPH

H ypertension is the most important modifiable risk factor


for stroke.1,2 It is estimated that 25% or more of strokes
may be attributable to hypertension. Because many patients
ICH presenting within 3 hours of symptom onset have a
significant expansion of the hematoma over the next 20
hours.7 Initial hematoma volume and hematoma expansion
with stroke have mild hypertension or prehypertension, we have are powerful predictors of mortality after ICH.8 Some studies
shifted our focus and now think of stroke on a continuum of risk have suggested an association between high BP and hema-
based on blood pressure (BP) level rather than on a threshold toma expansion and BP is often lowered under the assump-
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

effect.3 Because high BP may not exist in isolation, a wider tion that high BP promotes hematoma expansion.9
definition of hypertension has been proposed that also takes However, 2 recent studies question this relationship. In a
into account the absolute risk of cardiovascular events and series of 65 prospectively studied patients with ICH pres-
associated metabolic factors or early disease markers.3 enting within 3 hours, 37% had significant hematoma en-
Lowering BP reduces the risk of stroke. Epidemiological largement within 24 hours. Neither baseline nor peak BP was
studies have shown that for each 10 mm Hg lower systolic significantly associated with hematoma growth.10 In another
blood pressure (SBP), there is a decrease in risk of stroke of pooled analysis of 218 patients with onset of symptoms ⬍3
approximately one third in persons aged 60 to 79 years. This hours, hematoma volume was measured at presentation and
association is continuous down to levels of at least 115/ 20 to 24 hours later. Percentage hematoma growth, initial
75 mm Hg and is consistent across sexes, regions, stroke ICH volume, Glasgow Coma Scale score, and presence of
subtypes, and for fatal and nonfatal events.4 Lowering dia- intraventricular hemorrhage were all associated with in-
stolic blood pressure (DBP) was once the main target to creased mortality; however, BP was not.8
achieve stroke and other cardiovascular event reduction, but Nonetheless, there may be other reasons to lower BP.
SBP has now become the target.3 As recently shown, even the Hypertensive patients with ICH may have heart failure or
elderly with sustained SBP elevation may gain from BP elevated cardiac troponin in which lowering BP might be
reduction in relation to less fatal or nonfatal stroke, death, and helpful.11
heart failure.5 The argument against lowering BP in acute ICH is based
Although the role of longer-term BP control to improve on the possible existence of a perihematomal ischemic zone.
outcomes in patients with stroke is undisputed, BP manage- Recent studies, however, indicate that low blood flow around
ment immediately after a stroke remains controversial. In an the hematoma may be a consequence of reduced cerebral
effort to resolve this controversy, several pilot clinical trials metabolism in this area rather than a primary reduction of blood
have been initiated. In this review, we discuss the results of flow.12 In addition, chronic hypertensives (due to a shift in the
some of these trials and available evidence-based guidelines autoregulatory curve) and patients with increased intracranial
for BP control in the settings of acute ischemic and hemor- pressure (ICP; due to lowered cerebral perfusion pressure) may
rhagic stroke (excluding subarachnoid hemorrhage) and in develop cerebral ischemia if BP is acutely lowered.
recurrent stroke prevention.
The Evidence
Blood Pressure Management After Previous studies on BP management in ICH have been limited
Intracerebral Hemorrhage by small sample sizes or retrospective designs. Three prospec-
Patients with intracerebral hemorrhage (ICH) often have tive pilot trials on acute BP reduction after ICH have recently
elevated BP.6 Approximately one third of all patients with concluded and the results were presented at the International

Received July 14, 2008; final revision received November 10, 2008; accepted November 19, 2008.
From Neurological Intensive Care (V.A.) and the Center for Stroke Research (P.B.G.), Department of Neurology and Rehabilitation, University of
Illinois at Chicago, Chicago, Ill.
Correspondence to Venkatesh Aiyagari, MBBS, DM, Co-Director, Neurological Intensive Care, Department of Neurology and Rehabilitation,
University of Illinois at Chicago, 912 S Wood Street, Room 855N, Chicago, IL 60612. E-mail aiyagari@uic.edu
(Stroke. 2009;40:2251-2256.)
© 2009 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.108.531574

2251
2252 Stroke June 2009

Stroke Conference in 2008. It should be pointed out that trials Table 1. AHA/ASA Recommendations for BP Management in
were not powered to assess clinical efficacy. Acute Cerebral Hemorrhage16
The Antihypertensive Treatment of Acute Cerebral Hem- 1. If SBP is ⬎200 mm Hg or MAP is ⬎150 mm Hg, consider aggressive
orrhage study was a multicenter US study addressing the reduction of BP.
tolerability and safety of intravenous nicardipine infusion for 2. If SBP is ⬎180 mm Hg or MAP is ⬎130 mm Hg and ICP may be
18 to 24 hours postictus in patients with ICH with a of SBP elevated, consider monitoring ICP and reducing BP to keep cerebral
⬎200 mm Hg presenting within 6 hours of symptoms.13 Three perfusion pressure between 60 and 80 mm Hg.
SBP goals (170 to 200, 140 to 170, and 110 to 140 mm Hg) were 3. If SBP is ⬎180 mm Hg or MAP is ⬎130 mm Hg and there is no
targeted. The study moved to a lower treatment target if there evidence of or suspicion of elevated ICP, consider modest BP reduction
were no safety concerns at the higher target. Fifty-eight (eg, MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg).
patients (18, 20, and 20 in each target group, respectively)
with relatively small hematomas (mean volume ⬍20 mL)
sence of definitive data, the American Heart Association/
were enrolled. There was no difference in 3-month mortality
American Stroke Association (AHA/ASA) guidelines suggest
between the groups and the safety-stopping rule was not
maintaining a cerebral perfusion pressure of 60 to 80 mm Hg
activated in any tier.13 In a larger Asian study, Intensive blood
in patients with possible increased ICP and a BP of 160/90 or
pressure reduction in acute cerebral hemorrhage trial, hyper-
a MAP of 110 mm Hg in other patients.16 Recent data from
tensive patients (SBP 150 to 220 mm Hg) with an acute ICH
pilot trials indicate that a more aggressive BP reduction in
within 6 hours of symptom onset were randomized to
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

patients with relatively small hematomas to normotensive


antihypertensive treatment to a target of 140 mm Hg (intensive
levels soon after an ICH is quite well tolerated.13,14 We await
group; n⫽203) or 180 mm Hg (guideline group; n⫽201) for 7
the results of planned larger clinical trials to see if this approach
days or until hospital discharge.14 Most of the patients were
will result in improved outcomes.
residents of China (95%), in a good clinical grade (median
Glasgow Coma Scale 14) with small deep ganglionic hema- How Fast Should Blood Pressure Be Lowered?
tomas. Compared with the guideline group, the intensive Answer: results of small studies suggest that rapidly lowering
group showed significantly lower mean proportional hema- MAP by approximately 15% does not lower cerebral blood
toma growth at 24 hours (13.7% versus 36.3%; P⫽0.04). flow, whereas reductions of ⬎20% can do so.17,18 Therefore,
However, this difference was not significant after adjustment if BP-lowering is considered, current guidelines suggest
for initial hematoma volume and time from onset of ICH to cautious lowering of BP by no more that 20% in the first 24
CT scan. There was no significant difference in adverse event hours.16,19
rate or outcome at 90 days.14 The Control of Hypertension
and Hypotension Immediately Post-Stroke (CHHIPS) pilot What Antihypertensive Agents Are Appropriate for Use in
trial is discussed subsequently. Notably, this trial included the Acute Setting?
patients with ischemic and hemorrhagic stroke. The small Answer: Short and rapidly acting intravenous antihyper-
number of patients with ICH (n⫽25) makes interpretation of tensive agents are preferred. In the United States, labetalol,
the results in this stroke subtype quite difficult.15 The results hydralazine, esmolol, nicardipine, enalapril, nitroglycerin,
of these 3 trials indicate that intensive BP-lowering in the and nitroprusside have been recommended.16 Intravenous
acute phase is clinically feasible and well tolerated. Larger urapidil is also used in Europe.19 Large studies comparing
trials are planned to test the hypothesis that hematoma various antihypertensives are not available. Sodium nitro-
expansion can be limited by acute treatment of hypertension. prusside and nitroglycerin should be used with caution
because these agents can potentially increase ICP.
Questions and Answers About Blood Pressure
Management After Acute Guidelines
Intracerebral Hemorrhage In Table 1, we summarize the AHA/ASA guidelines on the
What Blood Pressure Level Is Considered to Be Too High management of hypertension in patients with ICH.16 The
and Requiring Immediate Reduction? European Stroke Initiative, Canadian Hypertension Educa-
Answer: Despite absence of definitive supportive evidence, tion Committee, and the International Society of Hyper-
some experts believe that a SBP of ⬎180 mm Hg or a mean tension have also published guidelines that are referenced
arterial pressure (MAP) of ⬎130 mm Hg would warrant for review.19 –21
immediate lowering.16 In the presence of conditions such as
acute heart failure, hypertensive encephalopathy, active cardiac Blood Pressure Management After Acute
ischemia, and so on, lower BP targets may be appropriate.
Ischemic Stroke
What Is the Appropriate Target Blood Pressure in An elevated BP, that often declines spontaneously, is seen on
Patients With ICH? presentation in most patients with acute ischemic stroke.22
Answer: Immediately after an ICH, it is perhaps more Several studies have emphasized the effect of elevated BP on
appropriate to tailor the target BP to each patient rather than outcome after stroke, but the results are inconsistent.22,23 In
using a “one size fits all” approach. The possibility of increased the International Stroke Trial, the largest of these studies, there
ICP and a history of chronic untreated hypertension should be appeared to be a U-shaped relationship between BP and mortal-
considered while choosing the target. Recognizing the ab- ity. Early death increased by 17.9% for every 10 mm Hg below
Aiyagari et al Stroke and Blood Pressure Management 2253

a SBP of 150 mm Hg and by 3.8% for every 10 mm Hg above Table 2. AHA/ASA Recommendations for BP Management in
a SBP of 150 mm Hg.24 Acute Ischemic Stroke27
1. Patients eligible for treatment with intravenous thrombolytics or other
The Evidence acute reperfusion intervention and SBP ⬎185 mm Hg or DBP
There is a paucity of clinical trial data addressing BP ⬎110 mm Hg should have BP lowered before the intervention. A
management in the setting of an acute ischemic stroke. A persistent SBP of ⬎185 mm Hg or a DBP ⬎110 mm Hg is a
Cochrane review of 218 patients from 5 clinical trials contraindication to intravenous thrombolytic therapy. After reperfusion
therapy, keep SBP ⬍180 mm Hg and DBP ⬍105 mm Hg for at least 24
concluded that the data were insufficient to make a firm hours.
recommendation on the value of acute BP reduction after
2. Patients who have other medical indications for aggressive treatment of
a stroke.25 In the Acute Candesartan Cilexitil Evaluation in BP should be treated.
Stroke Survivors trial, hypertensive patients with acute 3. For those not receiving thrombolytic therapy, BP may be lowered if it is
stroke (symptom onset ⬍72 hours) treated with Candesar- markedly elevated (SBP ⬎220 mm Hg or DBP ⬎120 mm Hg). A
tan for 7 days had a significantly improved outcome reasonable goal would be to lower BP by approximately 15% during the
compared with the placebo group. However, there was no first 24 hours after onset of stroke.
BP difference between the groups and therefore improved 4. In hypotensive patients, the cause of hypotension should be sought.
outcome cannot be attributed to a direct effect of lowering Hypovolemia and cardiac arrhythmias should be treated and in
exceptional circumstances, vasopressors may be prescribed in an attempt
BP. Moreover, this trial was powered to evaluate the safety
to improve cerebral blood flow.
rather than the efficacy of acute BP reduction.26
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

The CHHIPS pilot trial randomized patients with ischemic


or hemorrhagic stroke with a SBP ⬎160 mm Hg to treatment Should Blood Pressure Be Elevated to Improve Cerebral
with lisinopril (n⫽58), labetalol (n⫽58), or placebo (n⫽63) Perfusion in Patients With Ischemic Stroke?
within 24 hours (later extended to 36 hours) of symptom Answer: A few small case series have shown neurological
improvement with induced hypertensive therapy. Studies are
onset. The target was a SBP of 145 to 155 mm Hg or a
underway to assess the usefulness of this form of therapy in
15 mm Hg fall. Active treatment resulted in a significant
patients with a diffusion–perfusion mismatch on MRI.29 In
difference in SBP without an increase in adverse events
the meantime, it is reasonable to try volume expansion and/or
compared with placebo. There was no difference in the
vasopressors in patients with hypotensive stroke or in patients
primary outcome measure with 61% of the active group
who have had a worsening of the neurological deficit in
dead/dependent at 2 weeks compared with 59% of the association with a drop in BP.
placebo group. However, there was a borderline significant
difference in survival at 90 days (11 deaths in the active group Should Patients on Antihypertensive Agents Have Their
[10%] vs 12 deaths in the placebo group [20%], HR 0.4, 95% Medications Held or Continued?
CI 0.2–1.0, P⫽0.05). The results indicate that it is reasonable Answer: There are no substantial clinical data available to
to proceed with a larger trial to establish the efficacy of acute answer this question and a clinical trial is underway to
address this issue (Continue or stop poststroke antihyperten-
BP-lowering in improving outcome.15
sives study).30 The AHA/ASA guidelines recommend restart-
Questions and Answers on BP Management ing antihypertensives at 24 hours in previously hypertensive
Immediately After an Acute Ischemic Stroke neurologically stable patients unless contraindicated.27

Should Blood Pressure Be Lowered in Patients With Guidelines


Elevated BP After an Ischemic Stroke? In Table 2 we summarize AHA/ASA guidelines.27 The Euro-
Answer: As per the AHA/ASA guidelines, it is recommended pean Stroke Organization guidelines are referenced for review.31
that before intravenous thrombolytic treatment, BP should be
lowered if ⬎185 mm Hg systolic or ⬎110 mm Hg diastolic. Blood Pressure Management and Prevention
After thrombolytic treatment, SBP should be kept of Recurrent Stroke
⬍180 mm Hg and DBP ⬍105 mm Hg. Intravenous labetalol,
The Evidence
nitropaste, nicardipine infusion, and, if BP remains elevated,
There is substantial evidence to support BP-lowering for
sodium nitroprusside are the recommended agents.27 Despite prevention of a first stroke; however, few trials have focused
the absence of supporting evidence, these recommendations on antihypertensive therapy for recurrent stroke prevention.
are often applied to patients receiving other forms of reper- Two recent studies that addressed this issue are Perindopril
fusion therapy (eg, intra-arterial thrombolysis, clot retrieval, Protection Against Recurrent Stroke Study (PROGRESS) and
and so on).27 Patients with other indications for BP-lowering Morbidity and Mortality after Stroke, and Eprosartan com-
such as acute heart failure, aortic dissection, and so on should pared with Nitrendipine for Secondary Prevention study
have the BP lowered. One should be cautious about abruptly (MOSES).32,33 A third trial, Prevention Regimen for Effec-
lowering BP in other patients due to the risk of worsening tively avoiding Second Strokes (PRoFESS), was recently
cerebral ischemia.28 Guidelines suggest withholding antihyper- published.34
tensive agents in these patients unless the DBP is ⬎120 mm Hg PROGRESS was a well-conceived and conducted clinical
or the SBP is ⬎220 mm Hg and limiting the drop in BP during trial of BP-lowering. A total of 6105 patients with a history of
the first 24 hours by approximately 15%.27 stroke or transient ischemic attack within the past 5 years
2254 Stroke June 2009

were eligible to be randomized to perindopril, an angioten- analysis suggested that the effect of telmisartan might be
sin-converting enzyme inhibitor with or without indapamide, time-dependent because there was no significant difference in
a thiazide-like diuretic, versus placebo as add-on therapy. In event rates in the first 6 months after randomization for the
the perindopril-based treatment group, BP was lowered by primary outcome (a modest increase in events was noted)
approximately 9/4 mm Hg, and there was a statistically signifi- with a difference favoring telmisartan emerging later. Had the
cant 28% relative risk reduction for the primary outcome, total trial been carried out for a longer period of time, it has been
stroke, as well as other important results in relation to major speculated that a significant benefit of telmisartan may have
vascular event reduction.32 Overall, with greater lowering of been noted. Finally, a nonsignificant trend for a lower rate of
BP, the risk reduction benefit increased for major outcome new-onset diabetes mellitus was associated with telmisartan
end points. There has been debate about the value of perindopril treatment (1.2% versus 1.5%; P⫽0.10).
alone in reducing major vascular events because BP was only
reduced by approximately 5/3 mm Hg in this group corre- Questions and Answers About BP Management
sponding to a 5% nonsignificant reduction in total stroke. A for Recurrent Stroke Prevention
significant reduction of stroke risk was only achieved for the When Is It Safe to Lower BP After an Acute Ischemic
perindopril and indapamide combination as demonstrated in Stroke for the Purpose of Recurrent Stroke Prevention?
stratified analysis.1 A key message derived from PROGRESS Answer: While awaiting the arrival of more definitive data,
is that greater BP-lowering may be associated with more the available evidence suggests that it might be reasonable to
significant benefit in terms of reducing major vascular events. start oral antihypertensives as soon as 24 to 72 hours after
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

In MOSES, 1405 patients from general-type medicine onset of symptoms provided there are no contraindications
clinics with a history of cerebrovascular events were random- such as a presumed hemodynamic mechanism of stroke.26,30
ized in an open-label trial to either the angiotensin receptor The AHA/ASA guideline supports BP-lowering therapy as
blocker, eprosartan, or the calcium channel blocker, nitrendip- soon as 24 hours after acute ischemic stroke.27
ine.33 Approximately 75% of the subjects reached the treatment
goal of BP ⬍140/90 mm Hg, and by the end of the trial, BPs What Is the Target BP Goal?
Answer: The precise target goal is not definitively known. In
were nearly the same in the 2 groups. Although not the primary
the PROGRESS trial, BP was lowered by approximately 10/
end point, fatal and nonfatal cerebrovascular events were
5 mm Hg, and this BP target has been suggested as a reasonable
statistically significantly reduced favoring the eprosartan
one for patients according to the AHA/ASA guideline.35 How-
treatment group, as was the primary end point, combined
ever, there is variability of absolute BP level and response
cerebrovascular and cardiovascular events and noncardiovas-
to BP-lowering by the patient, especially when age is taken
cular death. The interpretation of these results have been
into account, and this must be considered before attempting to
questioned because of the inclusion of transient ischemic
lower BP. A reasonable goal, if it can be safely achieved after
attacks (which may not be as clinically relevant as completed
ischemic stroke, is the Seventh Report of the Joint National
strokes) in the primary composite end point and secondary
Committee on Prevention, Detection, Evaluation, and Treat-
end points for all cerebrovascular events.
ment of High Blood Pressure (JNC 7) target of ⬍140/
In PRoFESS, 20 332 patients with ischemic stroke were
90 mm Hg for uncomplicated hypertensive patients and
randomized to either the angiotensin receptor blocker, 80
⬍130/80 mm Hg for those with diabetes mellitus or chronic
mg/day telmisartan (n⫽10 146), or placebo (n⫽10 186) on a
kidney disease.36 Persons without hypertension may also
background of standard antihypertensive therapy as part of a
benefit from BP-lowering in relation to recurrent stroke
2⫻2 factorial design study, which also included aspirin plus
prevention.35
extended-release dipyridamole plus versus clopidogrel. Dur-
ing the average follow-up period of 2.5 years, mean BP was Which BP-Lowering Agent Is Most Effective?
3.8/2.0 mm Hg lower in the telmisartan treatment, although at Answer: In general, all major classes of BP-lowering agents may
1 month and 1 year, the between-group difference in SBP was diminish recurrent stroke risk. Although some studies have
5.4 and 4.0 mm Hg, respectively, showing that the BP suggested that angiotensin-converting enzyme inhibitors and
difference favoring telmisartan had narrowed over time. angiotensin receptor blockers may be more effective in recur-
There was no significant interaction between the BP-lowering rent stroke prevention than other antihypertensive agents, this
or antiplatelet arms of the study. Overall, there were fewer assertion has not been validated in more recent studies. Thus
recurrent stroke events in the telmisartan treatment group far and based on somewhat limited data, the degree of
compared with the placebo group (8.7% versus 9.2%; hazard BP-lowering may be more important than the agent used. The
ratio⫽0.95; 95% CI, 0.87 to 1.01), but this did not reach choice of the antihypertensive agent should probably depend
statistical significance (P⫽0.23).34 Major cardiovascular more on the associated medical conditions rather than any
events were less frequent in the telmisartan group (13.5% specific cerebrovascular protective effects of a specific class
versus 14.4%; hazard ratio⫽0.94; 95% CI, 0.87 to 1.01), but of antihypertensive agents. ␤-blockers may have a reduced
this was not a statistically significant difference (P⫽0.11). Of ability to protect against stroke (particularly atenelol), may
note, hypotensive symptoms (3.9% versus 1.8%; P⬍0.001) favor weight gain, and cause dyslipidemia and impaired
and syncope (0.2% versus 0.1%; P⫽0.004) led to discontin- glycemic control. Therefore, persons at risk for or with
uation of study medication more frequently in the telmisartan multiple metabolic factors may not be good candidates for
group as did diarrhea (0.7% versus 0.4%; P⫽0.02) and ␤ -blocker administration unless they are vasodilator
nausea (1.0% versus 0.7%; P⫽0.01). Post hoc exploratory ␤-blockers, which may not be associated with these latter side
Aiyagari et al Stroke and Blood Pressure Management 2255

Table 3. AHA/ASA Recommendations for BP Management for 5. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D,
Prevention of Recurrent Stroke35 Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A,
Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ; HYVET Study
1. Antihypertensive treatment is indicated to prevent recurrent stroke and Group. Treatment of hypertension in patients 80 years of age or older.
other vascular events; for ischemic stroke, treatment is initiated beyond N Engl J Med. 2008;358:1887–1898.
the hyperacute stroke period. 6. Fogelholm R, Avikainen S, Murros K. Prognostic value and determinants
of first-day mean arterial pressure in spontaneous supratentorial intrace-
2. The absolute target BP level is uncertain and should be individualized by rebral hemorrhage. Stroke. 1997;28:1396 –1400.
patient; benefit may be noted with an average BP drop of 10/5 mm Hg. 7. Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L,
3. Lifestyle modifications are included as part of a comprehensive approach. Spilker J, Duldner J, Khoury J. Early hemorrhage growth in patients with
intracerebral hemorrhage. Stroke. 1997;28:1–5.
4. Choice of antihypertensive drug(s) remains uncertain; a diuretic or
8. Davis SM, Broderick J, Hennerici M, Brun NC, Diringer MN, Mayer SA,
diuretic plus an angiotensin-converting enzyme inhibitor is a reasonable Begtrup K, Steiner T; Recombinant Activated Factor VII Intracerebral
choice; however, compelling indications may exist for a specific class of Hemorrhage Trial Investigators. Hematoma growth is a determinant of
antihypertensive and use of the JNC 7 report is recommended. mortality and poor outcome after intracerebral hemorrhage. Neurology.
2006;66:1175–1181.
9. Ohwaki K, Yano E, Nagashima H, Hirata M, Nakagomi T, Tamura A.
effects. Thiazide diuretics also may have dyslipidemic and Blood pressure management in acute intracerebral hemorrhage: rela-
tionship between elevated blood pressure and hematoma enlargement.
diabetogenic effects when used at high doses, although this
Stroke. 2004;35:1364 –1367.
has been questioned by the findings of the Antihypertensive 10. Jauch EC, Lindsell CJ, Adeoye O, Khoury J, Barsan W, Broderick J,
and Lipid-Lowering Treatment to Prevent Heart Attack trial Pancioli A, Brott T. Lack of evidence for an association between hemo-
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

that failed to support the preference for calcium channel dynamic variables and hematoma growth in spontaneous intracerebral
hemorrhage. Stroke. 2006;37:2061–2065.
blockers, ␣-blockers, or angiotensin-converting enzyme in- 11. Hays A, Diringer MN. Elevated troponin levels are associated with higher
hibitors compared with thiazide-type diuretics in patients mortality following intracerebral hemorrhage. Neurology. 2006;66:
with metabolic syndrome.37 The AHA/ASA guideline recom- 1330 –1334.
mends consideration of a diuretic in combination with an 12. Zazulia AR, Diringer MN, Videen TO, Adams RE, Yundt K, Aiyagari V,
Grubb RL Jr, Powers WJ. Hypoperfusion without ischemia surrounding
angiotensin-converting enzyme inhibitor.35 acute intracerebral hemorrhage. J Cereb Blood Flow Metab. 2001;21:
804 – 810.
Guidelines 13. Qureshi AI. Acute blood pressure management—the North American
Table 3 lists recommendations for BP management according perspective. Update on cerebral hemorrhage trials session. Presented at
the International Stroke Conference; New Orleans; February 20, 2008.
to AHA/ASA guidelines.35 Select recent guides from other Available at: www.scienceondemand.org/stroke2008/sessions/player.
regions are referenced.31,38 The JNC 7 is an excellent guide html?sid⫽08020172.758. Accessed July 4, 2008.
for overall BP management.36 14. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E,
Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW,
Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J,
Conclusion INTERACT Investigators. Intensive blood pressure reduction in acute
The management of hypertension in the setting of an acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet
stroke is a vexing clinical problem. Recent data suggest that Neurol. 2008;7:391–399.
15. Potter JF, Robinson TG, Ford GA, Mistri A, James M, Chernova J, Jagger
lowering BP in acute ICH is probably safe; however, it remains
C. Controlling hypertension and hypotension immediately poststroke
to be seen if this decreases hematoma expansion or improves (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial.
outcome. Blood pressure management in acute ischemic stroke Lancet Neurol. 2009;8:48 –56.
remains problematic and questions such as when to start anti- 16. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D,
Mayberg M, Morgenstern L, Ogilvy CS, Vespa P, Zuccarello M.
hypertensives and by how much to reduce BP are yet to be American Heart Association, American Stroke Association Stroke
resolved. Although lowering BP is effective for recurrent stroke Council, High Blood Pressure Research Council, Quality of Care and
prevention, the degree of BP reduction may be more important Outcomes in Research Interdisciplinary Working Group. Guidelines for
than the class of the agent used. the management of spontaneous intracerebral hemorrhage in adults: 2007
update: a guideline from the American Heart Association/American
Stroke Association Stroke Council, High Blood Pressure Research
Disclosures Council, and the Quality of Care and Outcomes in Research Interdisci-
P.B.G. serves on and receives honoraria for participation on the plinary Working Group. Stroke. 2007;38:2001–2023.
Aliskiren safety committee for Norvartis, steering committee for 17. Powers WJ, Zazulia AR, Videen TO, Adams RE, Yundt KD, Aiyagari V,
Bayer for the ARRIVE trial, steering committee for Boehringer Grubb RL Jr, Diringer MN. Autoregulation of cerebral blood flow sur-
Ingelheim for the PRoFESS trial, steering committee for Brainsgate rounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology.
for a device to improve brain blood flow, and adjudications com- 2001;57:18 –24.
mittees for Myriad, TAP and Pfizer; and has lectured for and 18. Kuwata N, Kuroda K, Funayama M, Sato N, Kubo N, Ogawa A. Dys-
autoregulation in patients with hypertensive intracerebral hemorrhage. A
received honoraria from diaDexus and Boehringer Ingelheim. V.A.
SPECT study. Neurosurg Rev. 1995;18:237–245.
has received honoraria from Boehringer-Ingelheim.
19. European Stroke Initiative Writing Committee, Writing Committee for
the EUSI Executive Committee, Steiner T, Kaste M, Forsting M,
References Mendelow D, Kwiecinski H, Szikora I, Juvela S, Marchel A, Chapot R,
1. Gorelick PB. New horizons for stroke prevention: PROGRESS and Cognard C, Unterberg A, Hacke W. Recommendations for the man-
HOPE. Lancet Neurol. 2002;1:149 –156. agement of intracranial haemorrhage—part I: spontaneous intracerebral
2. Pedelty L, Gorelick PB. Chronic management of blood pressure after haemorrhage. The European Stroke Initiative Writing Committee and the
stroke. Hypertension. 2004;44:1–5. Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis.
3. Elliott WJ. Systemic hypertension. Curr Probl Cardiol. 2007;32: 2006;22:294 –316.
201–259. 20. Bath P, Chalmers J, Powers W, Beilin L, Davis S, Lenfant C, Mancia G,
4. Lawes CM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and Neal B, Whitworth J, Zanchetti A; International Society of Hypertension
stroke: an overview of published reviews. Stroke. 2004;35:1024. Writing Group. International Society of Hypertension (ISH): statement on
2256 Stroke June 2009

the management of blood pressure in acute stroke. J Hypertens. 2003;21: 32. PROGRESS Collaborative Group. Randomised trial of a perindopril-based
665– 672. blood-pressure-lowering regimen among 6,105 individuals with previous
21. Boulanger JM, Hill MD, CHEP (Canadian Hypertension Educational stroke or transient ischaemic attack. Lancet. 2001;358:1033–1041.
Program). Hypertension and stroke: 2005 Canadian Hypertension Edu- 33. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K, Berger J,
cational Program recommendations. Can J Neurol Sci. 2005;32:403– 408. Zidek W, Dominiak P, Diener HC; MOSES Study Group. Morbidity and
22. Britton M, Carlsson A, de Faire U. Blood pressure course in patients with Mortality After Stroke, Eprosartan Compared with Nitrendipine for Sec-
acute stroke and matched controls. Stroke. 1986;17:861– 864. ondary Prevention: principal results of a prospective randomized con-
23. Okumura K, Ohya Y, Maehara A, Wakugami K, Iseki K, Takishita S. trolled study (MOSES). Stroke. 2005;36:1218 –1226.
Effects of blood pressure levels on case fatality after acute stroke. 34. Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA,
J Hypertens. 2005;23:1217–1223. Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BP, Chen
24. Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA; IST Collaborative ST, Cunha L, Dahlof B, De Keyser J, Donnan GA, Estol C, Gorelick P,
Group. Blood pressure and clinical outcomes in the International Stroke Gu V, Hermansson K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P,
Trial. Stroke. 2002;33:1315–1320. Roberts R, Skvortsova V, Teal P, Toni D, VanderMaelen C, Voigt T,
25. Blood pressure in Acute Stroke Collaboration (BASC). Interventions for Weber M, Yoon BW; PRoFESS Study Group. Telmisartan to prevent
deliberately altering blood pressure in acute stroke. Cochrane Database recurrent stroke and cardiovascular events. N Engl J Med. 2008;359:
Syst Rev. 2001;3:CD000039. 1225–1237.
26. Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, 35. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K,
Einhaupl K, Diener HC, Dominiak P; Acute Candesartan Cilexetil Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan
Therapy in Stroke Survivors Study Group. The ACCESS Study: eval- I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T.
uation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. American Heart Association, American Stroke Association Council on
Stroke. 2003;34:1699 –1703. Stroke, Council on Cardiovascular Radiology and Intervention, American
27. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Academy of Neurology. Guidelines for prevention of stroke in patients
Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern with ischemic stroke or transient ischemic attack: a statement for
Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF; American healthcare professionals from the American Heart Association/Am Stroke
Heart Association, American Stroke Association Stroke Council, Clinical
Association Council on Stroke: co-sponsored by the Council on Cardio-
Cardiology Council, Cardiovascular Radiology and Intervention Council,
vascular Radiology and Intervention: the American Academy of Neu-
Atherosclerotic Peripheral Vascular Disease and Quality of Care
rology affirms the value of this guideline. Stroke. 2006;37:577– 617.
Outcomes in Research Interdisciplinary Working Groups. Guidelines for
36. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr,
the early management of adults with ischemic stroke: a guideline from the
Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. National Heart,
American Heart Association/American Stroke Association Stroke
Lung, and Blood Institute Joint National Committee on Prevention,
Council, Clinical Cardiology Council, Cardiovascular Radiology and
Detection, Evaluation, and Treatment of High Blood Pressure, National High
Intervention Council, and the Atherosclerotic Peripheral Vascular Disease
Blood Pressure Education Program Coordinating Committee. The Seventh
and Quality of Care Outcomes in Research Interdisciplinary Working
Report of the Joint National Committee on Prevention, Detection, Eval-
Groups: the Am Academy of Neurology affirms the value of this
uation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA.
guideline as an educational tool for neurologists. Stroke. 2007;38:
1655–1711. 2003;289:2560–2572.
28. Fischberg GM, Lozano E, Rajamani K, Ameriso S, Fisher MJ. Stroke 37. Wright JT Jr, Harris-Haywood S, Pressel S, Barzilay J, Baimbridge C,
precipitated by moderate blood pressure reduction. J Emerg Med. 2000; Bareis CJ, Basile JN, Black HR, Dart R, Gupta AK, Hamilton BP,
19:339 –346. Einhorn PT, Haywood LJ, Jafri SZ, Louis GT, Whelton PK, Scott CL,
29. Wityk RJ. Blood pressure augmentation in acute ischemic stroke. Simmons DL, Stanford C, Davis BR. Clinical outcomes by race in
J Neurol Sci. 2007;261:63–73. hypertensive patients with and without the metabolic syndrome: Antihy-
30. Lewin S. Continue or stop post-stroke antihypertensives study (COSSACS). pertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
Principal Investigators: Professor TG Robinson, Professor JF Potter. 2008. (ALLHAT). Arch Intern Med. 2008;168:207–217.
Available at: www.le.ac.uk/cv/research/COSSACS/COSSACShome.html. 38. Kjellstrom T, Norrving B, Shatchkute A. Helsingborg Declaration 2006
Accessed July 4, 2008. on European stroke strategies. Cerebrovasc Dis. 2007;23:231–241.
31. European Stroke Organisation (ESO) Executive Committee, ESO Writing
Committee. Guidelines for management of ischaemic stroke and transient KEY WORDS: acute stroke 䡲 blood pressure 䡲 hypertension 䡲 intracerebral
ischaemic attack 2008. Cerebrovasc Dis. 2008;25:457–507. hemorrhage 䡲 recurrent stroke
Management of Blood Pressure for Acute and Recurrent Stroke
Venkatesh Aiyagari and Philip B. Gorelick

Stroke. 2009;40:2251-2256; originally published online April 23, 2009;


Downloaded from http://stroke.ahajournals.org/ by guest on January 24, 2017

doi: 10.1161/STROKEAHA.108.531574
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2009 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/40/6/2251

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.

Reprints: Information about reprints can be found online at:


http://www.lww.com/reprints

Subscriptions: Information about subscribing to Stroke is online at:


http://stroke.ahajournals.org//subscriptions/