Hypertension Journal

Show Contents

Management of Blood Pressure during Acute Stroke:A Narrative Review
  JOHTN
HYPERTENSIVE CRISIS
Management of Blood Pressure during Acute Stroke:
A Narrative Review
1Imran Rizvi, 2Ravindra K Garg, 3Hardeep S Malhotra, 4Neeraj Kumar, 5Manan M Mehta, 6Ravi Uniyal, 7Shweta Pandey
1,4,6,7Assistant Professor, 2Professor, 3Additional Professor
5Senior Resident
1-7Department of Neurology, King George's Medical UniversityLucknow, Uttar Pradesh, India
Corresponding Author: Ravindra K Garg, Professor, Departmentof Neurology, King George's Medical University, Lucknow, UttarPradesh, India
Phone: +919335901790
e-mail: garg50@yahoo.com
 
ABSTRACT
Hypertension is among the most important risk factors for theoccurrence of stroke. Acute stroke patients commonly have anelevated blood pressure (BP), and maintaining an appropriatelevel of BP is a crucial step in the successful management ofacute stroke. In this article, we review various trial and publishedguidelines for the management of hypertension during intracerebralhemorrhage (ICH) and acute ischemic stroke. Patients withICH were found to have systolic BP (SBP) in the range of 150 to220 mm Hg and need acute lowering of SBP to less than 140 mmHg. It is safe to do so if there are no contraindications. If a patientwith ICH presents with an SBP of more than 220 mm Hg, then theBP should be lowered aggressively using intravenous infusionalong with frequent monitoring. Patients of acute ischemic stroke,who have BP >185/110 mm Hg, should have their BP rapidlycontrolled, if they are being considered for thrombolytic therapy.Injectable labetalol, nicardipine, hydralinzine, and enalaprilat areconsidered appropriate for acute management of elevated BP inpatients with acute ischemic stroke. Patients of acute ischemicstroke with SBP > 180 to 230 mm Hg or diastolic BP (DBP)> 105 to 120 mm Hg should receive intravenous labetalol 10 mg;this can be followed by a continuous infusion at the rate of 2 to8 mg/min, if required. Nicardipine infusion is another alternativethat can be uptitrated according to the desired BP levels. Forsecondary prevention of ischemic stroke, BP lowering can bedone after first several days. The SBP > 140 mm Hg and DBP>90 mm Hg should be treated.
Keywords: Hypertension, Intracerebral hemorrhage, Ischemicstroke, Labetalol, Nicardipine.
How to cite this article: Rizvi I, Garg RK, Malhotra HS, Kumar N,Mehta MM, Uniyal R, Pandey S. Management of Blood Pressureduring Acute Stroke: A Narrative Review. Hypertens J2017;3(4):183-188.
Source of support: Nil
Conflict of interest: None
 
 

INTRODUCTION

Stroke is a global burden and a major cause of deathand disability across the world. Most of the strokesurvivors are dependent on their family members for activities of daily living. The costs of rehabilitation andlong-term treatment are also borne by the family.1,2 Theage-adjusted prevalence rates for stroke in India rangefrom 84 to 262/100,000 in rural areas and between 334and 442/100,000 in urban areas.3 Hypertension is amongthe most important modifiable risk factors for stroke.4,5More than 25% of all strokes are attributed to high BPor uncontrolled hypertension. Many patients of strokesuffer from mild hypertension as well as many fall intothe prehypertensive category. It is because of this observationmany studies and trials are now focusing on therisks based on BP levels, and not on absolute thresholdvalues.6 The majority of patients with hypertension havemany associated comorbid conditions like diabetes mellitus,dyslipidemia, obesity, metabolic syndrome, etc.Epidemiological studies have found out that loweringthe SBP by 10 mm Hg leads to reduction in the risk ofstroke.7 The SBP control is now considered to be moreimportant; previously the DBP lowering was consideredto be crucial.6 In a recent study, the importance of SBPcontrol is highlighted, even in elderly patients. The studyshowed that control of SBP in the elderly leads to reductionof stroke and risks of death and heart failure.8

 
Management of BP during acute stroke remains controversial.In this review, we will discuss BP managementduring acute stroke as well as BP control for secondaryprevention of recurrent stroke.

Management of BP in Patients of
Intracerebral Hemorrhage


The BP in patients of acute hemorrhagic stroke is oftenelevated because of several reasons: these factors includeraised intracranial pressure, premorbid hypertension,stress, and pain.9-11 Hematoma expansion that can leadto death and dependency is found to be associated withhigh SBP.11-14 About one-third of ICH patients presentingwithin 3 hours of symptom onset have a significantincrease in hematoma volume over the next 20 hours.15Baseline hematoma volume and its expansion are foundto be associated with increased risk of death followingICH.16 Hence, it is assumed that control of BP canreduce the chances of hematoma expansion. However,a couple of studies failed to demonstrate that BP loweringwill reduce hematoma expansion. In a series of 65patients of ICH presenting within 3 hours of symptom onset, baseline and peak BP were not found to be associatedwith hematoma expansion.17 In another series of218 patients of ICH, hematoma volume was not associatedwith high BP.16 However, despite the above observations,there are various reasons for BP control. Reducing BP inhypertensive patients lowers the incidence and preventshypertensive heart failure, which might be an addedcomplication in already critical patients of ICH.18 Othercomplications of uncontrolled hypertension like renalfailure, uremia, encephalopathy, and vasoconstrictionsyndromes can be prevented with control of BP. Thehypothesis against reducing BP in acute ICH is based onthe possible presence of a perihematomal ischemic zone.However, in recent studies, it has been found that the lowbloodflow around the hematoma may be a consequence ofreduction in the cerebral metabolism in that area, ratherthan hypoperfusion due to reduction in bloodflow.19 Anobservational study utilizing advanced neuroimagingfailed to demonstrate significant ischemic penumbra inICH patients.20 A randomized controlled trial utilizingcomputed tomography perfusion in small and mediumICH found no clinically significant reduction in the cerebralbloodflow within the perihematomal area, related toan early intensive BP lowering to an SBP of < 140 mm Hgwithin the early hours following ICH.21

Hypertension Journal, October-December, Vol 3, 2017 183

Imran Rizvi et al

Two large studies, antihypertensive treatment ofacute cerebral hemorrhage (ATACH) and the pilot phaseof intensive BP reduction in acute cerebral hemorrhage(INTERACT 1) found rapid lowering of SBP to < 140 mmHg to be safe.22,23 Even in the recent INTERACT 2 trial,it was observed that with acute BP lowering in eligiblepatients with elevated SBP, there was no increase indeath or serious adverse events.24 The INTERACT 2 trialobserved randomized patients of acute ICH with SBPbetween 150 and 220 mm Hg in two arms. The interventionarm received intensive lowering of BP, an SBP< 140 mm Hg within an hour of randomization; and thestandard arm targeted SBP < 180 mm Hg. The interventionarm showed a modest benefit in terms of primaryoutcome (death or major disability).24

Hence, the evidence available until date indicates thatearly intensive BP lowering in patients with ICH is safe,and it can lead to a modest reduction in mortality anddisability. There is scarcity of evidence in patients withICH presenting with SBP of >220 mm Hg. In Table 1, wesummarize the American Heart Association/AmericanStroke Association (AHA/ASA) guidelines for managementof BP in ICH patients.25

Management of BP during Acute Ischemic Stroke

The BP fluctuates significantly and has many clinicalconsequences during medical emergencies like acute ischemic stroke. Elevated BP is commonly encountered inpatients of acute ischemic stroke. The SBP > 139 mm Hgwas found in 77% patients and > 184 mm Hg in 15% inan observational study in patients on arrival to the emergencydepartment.10 Patients with a premorbid historyof hypertension were more likely to have higher BP onpresentation, as compared with those without history ofhypertension. Uncontrolled extreme BP adds to deteriorationdue to added complications like encephalopathy,cardiac failure, and renal insufficiency.

 
Table 1: AHA/ASA guidelines on BP managementin patients with ICH
Management of Blood Pressure during Acute Stroke:A Narrative Review

Moderate elevation of BP, theoretically, might be beneficialas it can lead to improvement of the cerebral perfusionof the penumbra, or it might prove to be harmfulby increasing edema and chances of hemorrhagictransformation. Hypotension is clearly detrimental, asit decreases perfusion to multiple organs including thebrain. Hence, it becomes a challenge for the clinicians tomanage the BP in a targeted range during acute ischemicstroke. No specific range of BP has been scientificallydetermined. It is likely that an ideal BP range duringacute ischemic stroke will depend on several factors likethe stroke subtype and other comorbidities.

Much literature has been published analyzing variousBP parameters in patients admitted with acute ischemicstroke and their clinical outcomes. Some studies demonstrateda U-shaped relationship between the baseline BP(at admission) and a favorable clinical outcome, with anoptimal SBP in the range of 121 to 200 mm Hg and DBPin the range of 81 to 110 mm Hg.26-29 However, elevatedBP during hospital stay was found to be associated withpoor clinical outcome in a linear fashion.30-32 Also, tonote, three studies showed poor outcome with reductionin BP26,32,33 while two studies could not demonstrate anyassociation between BP fluctuations and outcome.34,35The intravenous nimodipine West European stroke trial(INWEST) found that the reduction of BP using intravenousnimodipine was associated with poor clinicaloutcome at 21 days.36 In a placebo-controlled trial of350 patients, which tested oral nimodipine, given withinthe first 48 hours after ischemic stroke, it was observedthat SBP and DBP were significantly lowered in the nimodipine group. Functional outcome at 3 months wasnot different in both the groups, but the nimodipinegroup showed significant higher mortality.37 Anotherplacebo-controlled trial of therapy with angiotensinreceptor blocker candesartan,38 which included342 patients with high BP, had to be stopped prematurely.It was observed that patients receiving the active drughad significantly lower mortality and fewer vascularevents at the end of 12 months. The BP and Barthel IndexScore at 3 months were similar in both the study groups.38A larger trial showed that candesartan therapy led to areduction of mean BP by 7/5 mm Hg by day 7, but therewas no improvement in functional outcome.39 Anothertrial comparing lisinopril or labetalol vs placebo within36 hours after stroke onset found that the SBP droppedsignificantly in the two treatment groups (labetalol orlisinopril) than the placebo group. The drop in SBP wasseen more in the lisinopril group (by 14 mm Hg) than inthe labetalol group (by 7 mm Hg). This drop in BP in boththe active treatment groups was not associated with anycomplications. At 2 weeks, mortality or dependency wassimilar in both the active treatment groups, overall, andeven among the patient with ischemic stroke. However,at 3 months, mortality was significantly lower in thetwo active treatment groups (9.7%) than with placebo(20.3%, p = 0.05).40 The COSSACS study (continue orstop poststroke antihypertensive collaborative study)showed a comparison between two groups - one whereantihypertensive treatment was continued with anothergroup where the pre-existing antihypertensive drugswere discontinued during the time of hospitalization foracute ischemic stroke.41 In this study, patients of acuteischemic stroke within 48 hours onset and the last doseof antihypertensive medications were enrolled. Theywere maintained in two treatment arms for 2 weeks.Although the study was terminated prematurely, it wasobserved that continuation of antihypertensive drugsdid not reduce 2-week mortality or morbidity and wasnot associated with 6-month mortality or cardiovascularevent rates.41

 
184

Management of Blood Pressure during Acute Stroke

On the contrary, adding to the complexity of managementof BP in patients with acute ischemic stroke, somesmall pilot trials have carefully raised the BP in acutestroke patients, without any complications. Hence, thequestion remains unanswered as to what is the risk-benefit ratio for reducing or elevating the BP during acuteischemic stroke.

For this, we need larger trials with well-defined criteria.Hence, at this time, it is reasonable to believe theprevious recommendation which is to not reduce the BPduring the first 24 hours of acute ischemic stroke unlessand until the BP is >220/120 mm Hg or there is a concomitantspecific medical comorbidity that would benefit from reducing the BP. It is commonly seen that patients of acuteischemic stroke present with other associated conditionsor complications. Some conditions, such as heart failure,myocardial ischemia, renal insufficiency, and aortic dissectionmay exacerbate the BP. But, unfortunately, nooptimal approach or guidelines are available for suchconditions, when they coexist with cerebral ischemia,and, at present, goals of BP are based on clinical judgment.A reasonable approach might be to initially reduce theSBP by 15% and monitor for any neurological worseningrelated to the pressure lowering.
 
Management of BP in Ischemic Stroke Patients
Who are Eligible for Thrombolysis


With the advances in management of acute ischemicstroke and since the widespread use of thrombolytictherapy, management of BP in the emergency departmenthas gained significant importance. It is quitechallenging to control BP during an acute setting in thewindow period of < 3 hours of stroke onset. Table 2 showsspecific recommendations that have been establishedfor acute ischemic stroke patients, who are eligible forthrombolytic therapy.42 As per these guidelines, it isrecommended to bring the BP below 185/110 mm Hgto qualify for the fibrinolytic therapy with intravenoustissue plasminogen activator (rtPA). Once intravenousrtPA is administered, the BP should be maintained below180/105 mm Hg to reduce the risk of ICH. A large studypublished few years ago, which observed 11,080 patientsof acute ischemic stroke treated with intravenous rtPA,found associations between elevated BP and poor outcomesin this setting.43

Table 2: Potential approaches to arterial hypertension in acuteischemic stroke patients who are candidates for acute reperfusiontherapy
Management of Blood Pressure during Acute Stroke:A Narrative Review

Hypertension Journal, October-December, Vol 3, 2017 185

Imran Rizvi et al

Higher BP levels during the first 24 hours were associatedwith greater risk of symptomatic ICH in a linearfashion. However, too much reduction of BP was alsoharmful, establishing a U-shaped relation between theBP levels during initial 24 hours and death or dependencyat 90 days. The best outcomes were observed whenthe SBPs were in the range of 141 to 150 mm Hg. ArterialBP is a dynamic parameter. It is important to monitor itfrequently, especially during the initial period of acutestroke. It is prudent to identify the fluctuations and trendsof BP, which would be helpful in immediate managementand prevention of various complications. It is essential tokeep in mind the risk when lowering the BP in an acutestroke setting. This can be managed well when the BPis lowered in a well-controlled manner. Controlled BPlowering during acute stroke can best be achieved withintravenous antihypertensive drugs. The best approachis to individualize each patient as unique and selectionof the antihypertensive should be case based, as no singleoptimal medication to lower BP in all patients with acutestroke has been determined. Many stroke patients experiencedifficulty in swallowing in the initial period.

Long-term BP Control for Secondary
Prevention of Stroke


It is considered reasonable to temporarily discontinuepremorbid antihypertensive treatment at the time ofonset of acute ischemic stroke, due to swallowing impairmentas well as the response of these oral medicationsmay become unpredictable due acute stress conditions.44There are no established guidelines for the optimal timefor restarting or initiating long-term antihypertensivetherapy after acute ischemic stroke. It depends on manyfactors and varies from patient to patient and stroke characteristics.However, it is reasonable to initiate long-termantihypertensive therapy after the initial 24 hours fromstroke onset in most patients.40 Selection of long-termantihypertensives is done on individualized basis, as perpatient clinical condition, comorbidities, economic capability,and availability. BP Management and Prevention ofRecurrent Stroke Substantial evidence is available, whichsupports BP lowering after first stroke, for the preventionof recurrent strokes.

Two main studies addressing this issue are PerindoprilProtection against Recurrent Stroke Study (PROGRESS)and Morbidity and Mortality after Stroke, andEprosartan compared with Nitrendipine for SecondaryPrevention study (MOSES).45,46 Prevention Regimen forEffectively avoiding Second Strokes (PRoFESS) is anothertrial, published a few years ago.47 In the PROGRESStrial, 6,105 patients with a history of stroke or transientischemic attack within the past 5 years were enrolled. It was a well-conceived and well-conducted clinical trial ofBP lowering. Patients were randomized to perindopril,an angiotensin-converting enzyme inhibitor with orwithout indapamide, a thiazide-like diuretic vs placebo asadd-on therapy. The BP was lowered by about 9/4 mm Hgin the perindopril-based treatment group. There was astatistically significant 28% relative risk reduction for theprimary outcome, total stroke, as well as other importantresults in relation to major vascular event reductions. Asignificant reduction of stroke risk was only achieved forthe perindopril and indapamide combination as demonstratedin stratified analysis. Overall, it was found thatwith greater lowering of BP, the risk reduction benefitincreased for major outcome endpoints. A key messagederived from PROGRESS is that greater BP loweringmay be associated with more significant benefit in termsof reducing major vascular events.45 The MOSES trialwas an open-labeled trial in which patients were randomizedinto two groups. Totally, 1,405 patients witha history of cerebrovascular event were enrolled. Theywere randomized into either the angiotensin receptorblocker, eprosartan, or the calcium channel blocker,nitrendipine.46 Trial also included the patients of transientischemic event, hence questioning its outcome. However,approximately 75% of the subjects reached the treatmentgoal of BP 140/90 mm Hg, and it was found that the treatmentgroup with eprosartan therapy showed statisticallysignificant reduction in fatal and nonfatal cerebrovascularevents, as well as combined cerebrovascular andcardiovascular events and noncardiovascular deaths.In PRoFESS, 20,332 patients with ischemic stroke wererandomized to either the angiotensin receptor blocker,80 mg/day telmisartan (n = 10,146), or placebo (n = 10,186)on a background of standard antihypertensive therapy aspart of a 2 × 2 factorial design study, which also includedaspirin plus extended-release dipyridamole plus clopidogrel.On interpreting the results of the trial, we canfind that there was no significant interaction betweenthe BP-lowering or antiplatelet arms of the study. Overall,there were fewer recurrent stroke events in the telmisartantreatment group compared with the placebo group(8.7 vs 9.2%), but this did not reach statistical significance(p = 0.23).47 Major cardiovascular events were less frequentin the telmisartan group (13.5 vs 14.4%), but this wasnot a statistically significant difference (p = 0.11). Table 3lists recommendations for BP management according toAHA/ASA guidelines.48

 
CONCLUSION

Hypertension and stroke (ischemic or hemorrhagic) areclosely associated. It is a challenging task to manageBP fluctuations as well as extremely elevated BP in an cute setting of medical emergency of stroke. From theavailable data and studies, we can say that lowering BPin acute ICH is probably safe; however, it remains to beseen if this decreases hematoma expansion or improvesoutcome. In acute ischemic stroke, BP managementremains problematic and questions, such as when to startantihypertensives and by how much to reduce BP are yetto be resolved. However, BP control is prudent in patientsbeing considered for fibrinolytic therapy with intravenousrtPA. Lowering of BP is effective in preventing recurrentstroke. Combination of perindopril and indapamide hasbeen proven to be beneficial. In all given cases, it is best toindividualize treatment approaches for BP control duringan event of acute stroke.

 
186

Management of Blood Pressure during Acute Stroke

Table 3: AHA/ASA recommendations for BP management forprevention of recurrent stroke
Management of Blood Pressure during Acute Stroke:A Narrative Review

REFERENCES
  1. Bonita R, Beaglehole R. Stroke prevention in poor countries.Time for action. Stroke 2007 Nov;38:2871-2872.
  2. Pandian JD, Srikanth V, Read SJ, Thrift AG. Poverty and strokein India. Stroke 2007 Nov;38(11):3063-3069.
  3. Stroke fact sheet India. Available from: http://www.sancd.org/Updated%20Stroke%20Fact%20sheet%202012.pdf.
  4. Gorelick PB. New horizons for stroke prevention: PROGRESSand HOPE. Lancet Neurol 2002 Jul;1(3):149-156.
  5. Pedelty L, Gorelick PB. Chronic management of blood pressureafter stroke. Hypertension 2004 Jul;44(1):1-5.
  6. Elliott WJ. Systemic hypertension. Curr Probl Cardiol 2007Apr;32(4):201-259.
  7. Lawes CM, Bennett DA, Feigin VL, Rodgers A. Blood pressureand stroke: an overview of published reviews. Stroke 2004Apr;35(4):1024.
  8. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, DumitrascuD, Stoyanovsky V, Antikainen RL, Nikitin Y, AndersonC, et al. Treatment of hypertension in patients 80 years of ageor older. N Engl J Med 2008 May;358(18):1887-1898.
  9. Fogelholm R, Avikainen S, Murros K. Prognostic value anddeterminants of first-day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage. Stroke 1997 Jul;28(7):1396-1400.

 
  1. Qureshi AI, Ezzeddine MA, Nasar A, Suri MF, Kirmani JF,Hussein HM, Divani AA, Reddi AS. Prevalence of elevatedblood pressure in 563,704 adult patients with stroke presentingto the ED in the United States. Am J Emerg Med 2007Jan;25(1):32-38.
  2. Zhang Y, Reilly KH, Tong W, Xu T, Chen J, Bazzano LA, Qiao D,Ju Z, Chen CS, He J. Blood pressure and clinical outcomeamong patients with acute stroke in Inner Mongolia, China.J Hypertens 2008 Jul;26(7):1446-1452.
  3. Rodriguez-Luna D, Pineiro S, Rubiera M, Ribo M, Coscojuela P,Pagola J, Flores A, Muchada M, Ibarra B, Meler P, et al.Impact of blood pressure changes and course on hematomagrowth in acute intracerebral hemorrhage. Eur J Neurol 2013Sep;20(9):1277-1283.
  4. Sakamoto Y, Koga M, Yamagami H, Okuda S, Okada Y,Kimura K, Shiokawa Y, Nakagawara J, Furui E, Hasegawa Y,et al. Systolic blood pressure after intravenous antihypertensivetreatment and clinical outcomes in hyperacute intracerebralhemorrhage. Stroke 2013 Jul;44(7):1846-1851.
  5. Ohwaki K, Yano E, Nagashima H, Hirata M, Nakagomi T,Tamura A. Blood pressure management in acute intracerebralhemorrhage: relationship between elevated bloodpressure and hematoma enlargement. Stroke 2004 Jun;35(6):1364-1367.
  6. Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, SauerbeckL, Spilker J, Duldner J, Khoury J. Early hemorrhagegrowth in patients with intracerebral hemorrhage. Stroke1997 Jan;28(1):1-5.
  7. Davis SM, Broderick J, Hennerici M, Brun NC, Diringer MN,Mayer SA, Begtrup K, Steiner T; Recombinant ActivatedFactor VII Intracerebral Hemorrhage Trial Investigators.Hematoma growth is a determinant of mortality and pooroutcome after intracerebral hemorrhage. Neurology 2006Apr;66(8):1175-1181.
  8. Jauch EC, Lindsell CJ, Adeoye O, Khoury J, Barsan W,Broderick J, Pancioli A, Brott T. Lack of evidence for anassociation between hemodynamic variables and hematomagrowth in spontaneous intracerebral hemorrhage. Stroke2006 Aug;37(8):2061-2065.
  9. Hays A, Diringer MN. Elevated troponin levels are associatedwith higher mortality following intracerebral hemorrhage.Neurology 2006 May;66(9):1330-1334.
  10. Zazulia AR, Diringer MN, Videen TO, Adams RE, Yundt K,Aiyagari V, Grubb RL Jr, Powers WJ. Hypoperfusion withoutischemia surrounding acute intracerebral hemorrhage.J Cereb Blood Flow Metab 2001 Jul;21(7):804-810.
  11. Butcher KS, Baird T, MacGregor L, Desmond P, Tress B,Davis S. Perihematomal edema in primary intracerebral hemorrhageis plasma derived. Stroke 2004 Aug;35(8):1879-1885.
  12. Butcher KS, Jeerakathil T, Hill M, Demchuk AM, Dowlatshahi D,Coutts SB, Gould B, McCourt R, Asdaghi N, Findlay JM,et al. The intracerebral hemorrhage acutely decreasingarterial pressure trial. Stroke 2013 Mar;44(3):620-626.
  13. Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz-Flores S,Ehtisham A, Ezzeddine MA, Goldstein JN, Hussein HM,Suri MF, et al. Effect of systolic blood pressure reduction onhematoma expansion, perihematomal edema, and 3-monthoutcome among patients with intracerebral hemorrhage:results from the antihypertensive treatment of acute cerebralhemorrhage study. Arch Neurol 2010 May;67(5):570-576.

Hypertension Journal, October-December, Vol 3, 2017 187

Imran Rizvi et al

  1. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B,Heeley E, Skulina C, Parsons MW, Kim JS, et al. Intensiveblood pressure reduction in acute cerebral haemorrhage trial(INTERACT): a randomised pilot trial. Lancet Neurol 2008May;7(5):391-399.
  2. Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C,Lindley R, Robinson T, Lavados P, Neal B, et al. Rapid bloodpressurelowering in patients with acute intracerebral hemorrhage.N Engl J Med 2013 Jun;368(25):2355-2365.
  3. Hemphill JC, Greenberg SM, Anderson CS, Becker K, Bendok BR,Cushman M, Fung GL, Goldstein JN, Macdonald RL,Mitchell PH, et al. Guidelines for the management of spontaneousintracerebral hemorrhage. Stroke 2015 Jul;46(7):2032-2060.
  4. Castillo J, Leira R, Garcia MM, Serena J, Blanco M, Davalos A.Blood pressure decrease during the acute phase of ischemicstroke is associated with brain injury and poor strokeoutcome. Stroke 2004 Feb;35(2):520-526.
  5. Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA; IST CollaborativeGroup. Blood pressure and clinical outcomes in theInternational Stroke Trial. Stroke 2002 May;33(5):1315-1320.
  6. Okumura K, Ohya Y, Maehara A, Wakugami K, Iseki K,Takishita S. Effects of blood pressure levels on case fatalityafter acute stroke. J Hypertens 2005 Jun;23(6):1217-1223.
  7. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N,Synetos A, Manios E, Konstantopoulou P, Mavrikakis M.U-shaped relationship between mortality and admissionblood pressure in patients with acute stroke. J Intern Med2004 Feb;255(2):257-265.
  8. Aslanyan S, Fazekas F, Weir CJ, Horner S, Lees KR; GAINInternational Steering Committee and Investigators. Effectof blood pressure during the acute period of ischemic strokeon stroke outcome. Stroke 2003 Oct;34(10):2420-2425.
  9. Aslanyan S, Weir CJ, Lees KR; GAIN International SteeringCommittee and Investigators. Elevated pulse pressure duringthe acute period of ischemic stroke is associated with poorstroke outcome. Stroke 2004 Jun;35(6):e153-e155.
  10. Boreas AM, Lodder J, Kessels F, de Leeuw PW, Troost J.Prognostic value of blood pressure in acute stroke. J HumHypertens 2002 Feb;16(2):111-116.
  11. Oliveira-Filho J, Silva SC, Trabuco CC, Pedreira BB, Sousa EU,Bacellar A. Detrimental effect of blood pressure reductionin the first 24 hours of acute stroke onset. Neurology 2003Oct;61(8):1047-1051.
  12. Jensen MB, Yoo B, Clarke WR, Davis PH, Adams HR Jr.Blood pressure as an independent prognostic factor in acuteischemic stroke. Can J Neurol Sci 2006 Feb;33(1):34-38.
  13. Ritter MA, Kimmeyer P, Heuschmann PU, Dziewas R,Dittrich R, Nabavi DG, Ringelstein EB. Blood pressurethreshold violations in the first 24 hours after admission foracute stroke: frequency, timing, predictors, and impact onclinical outcome. Stroke 2009 Feb;40(2):462-468.
  14. Wahlgren NG, MacMahon DG, De Keyser JF, Indredavik B,Ryman T. Intravenous Nimodipine West European StrokeTrial (INWEST) of nimodipine in the treatment of acuteischaemic stroke. Cerebrovasc Dis 1994 May;4(3):204-10.

 
  1. Kaste M, Fogelholm R, Erila T, Palomaki H, Murros K,Rissanen A, Sarna S. A randomized, double-blind, placebocontrolledtrial of nimodipine in acute ischemic hemisphericstroke. Stroke 1994 Jul;25(7):1348-1353.
  2. Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J,Einhaupl K, Diener HC, Dominiak P; Acute CandesartanCilexetil Therapy in Stroke Survivors Study Group. TheACCESS study: evaluation of Acute Candesartan CilexetilTherapy in Stroke Survivors. Stroke 2003 Jul;34(7):1699-1703.
  3. Sandset EC, Bath PM, Boysen G, Jatuzis D, Korv J, Luders S,Murray GD, Richter PS, Roine RO, Terent A, et al. The angiotensin-receptor blocker candesartan for treatment of acutestroke (SCAST): a randomised, placebo-controlled, doubleblindtrial. Lancet 2011 Feb;377(9767):741-750.
  4. Potter JF, Robinson TG, Ford GA, Mistri A, James M,Chernova J, Jagger C. Controlling hypertension and hypotensionimmediately post-stroke (CHHIPS): a randomised,placebo-controlled, double-blind pilot trial. Lancet Neurol2009 Jan;8(1):48-56.
  5. Robinson TG, Potter JF, Ford GA, Bulpitt CJ, Chernova J,Jagger C, James MA, Knight J, Markus HS, Mistri AK, et al.Effects of antihypertensive treatment after acute stroke in theContinue or Stop Post-Stroke Antihypertensives CollaborativeStudy (COSSACS): a prospective, randomised, open,blinded-endpoint trial. Lancet Neurol 2010 Aug;9(8):767-775.
  6. Jauch EC, Saver JL, Adams HP, Bruno A, Demaerschalk BM,Khatri P, McMullan PW, Qureshi AI, Rosenfield K, Scott PA,et al. Guidelines for the early management of patients withacute ischemic stroke. Stroke 2013 Mar;44(3):870-947.
  7. Ahmed N, Wahlgren N, Brainin M, Castillo J, Ford GA,Kaste M, Lees KR, Toni D; SITS Investigators. Relationshipof blood pressure, antihypertensive therapy, and outcomein ischemic stroke treated with intravenous thrombolysis.Stroke 2009 Jul;40(7):2442-2449.
  8. Karachalios GN, Charalabopoulos A, Papalimneou V, Kiortsis D,Dimicco P, Kostoula OK, Charalabopoulos K. Withdrawalsyndrome following cessation of antihypertensive drugtherapy. Int J Clin Pract 2005 May;59(5):562-570.
  9. PROGRESS Collaborative Group. Randomised trial of aperindopril-based blood-pressure-lowering regimen among6,105 individuals with previous stroke or transient ischaemicattack. Lancet 2001 Sep;358(9287):1033-1041.
  10. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K,Berger J, Zidek W, Dominiak P, Diener HC; MOSES StudyGroup. Morbidity and mortality after stroke, eprosartancompared with nitrendipine for secondary prevention. Stroke2005 Jun;36(6):1218-1226.
  11. Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA,Palesch Y, Martin RH, Albers GW, Bath P, et al. Telmisartanto prevent recurrent stroke and cardiovascular events. N EnglJ Med 2008 Sep;359(12):1225-1237.
  12. Kernan WN, Ovbiagele B, Black HR, Bravata DM,Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL,Heck DV, et al. Guidelines for the prevention of stroke inpatients with stroke and transient ischemic attack. Stroke2014 Jan:45(7):2160-2236.

 
188