ISH statement 665 International Society of Hypertension (ISH): Statement on the Management of Blood Pressure in Acute Stroke International Society of Hypertension Writing Group The ISH statement on the management of blood pressure Journal of Hypertension 2003, 21:665–672 in acute stroke was ﬁnalized after presentation and discussion at the World Health Organization and Keywords: stroke, ischaemic stroke, primary intracerebral haemorrhage, International Society of Hypertension (WHO–ISH) Meeting blood pressure management, hypertension, International Society of Hypertension on Stroke and Blood Pressure, held in Melbourne, Australia, 5–7 December 2002. The meeting was conducted under the auspices of the Austin Hospital Correspondence and requests for reprints to Philip Bath, Stroke Association Professor of Stroke Medicine, Division of Stroke Medicine, University of Medical Research Foundation, Melbourne. J Hypertens Nottingham, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK. 21:665–672 & 2003 Lippincott Williams & Wilkins. Tel: +44 115 840 4792; fax: +44 115 840 4790 Introduction onset  and to settle over the ﬁrst weeks after stroke Research into improving the outcome of patients with [6–8]. Few patients have a low blood pressure, as acute stroke has largely focused on antithrombotic and deﬁned by systolic blood pressure , 100 mmHg. In- neuroprotective strategies and on health service reorga- deed, in the International Stroke Trial, less than 5% of nization with the establishment of Stroke Units for the patients with ischaemic stroke had a systolic blood care of patients in the acute phase of stroke. Whilst pressure , 120 mmHg . therapy with antiplatelet and thrombolytic drugs and management in a Stroke Unit have been shown to Primary intracerebral haemorrhage reduce combined death and dependency [1–3], anti- High blood pressure is present in approximately 80% of coagulation and neuroprotection have, so far, appeared patients with PICH [6–8], and tends to be higher than ineffective or hazardous . Physiological derangement, in patients with ischaemic stroke [12,13]. such as high blood pressure, hyperglycaemia, pyrexia and intracranial hypertension, is common in acute Pathophysiology of high and low blood stroke and associated with a poor outcome . There is pressure in acute stroke now a worldwide interest in trying to reduce poor There is no single explanation for high blood pressure outcomes after stroke through effective management of in acute stroke. Many contributing factors have been these conditions. This document reviews current know- suggested and probably apply variably in different ledge on blood pressure in acute ischaemic stroke and stroke types (ischaemic stroke, PICH) and subtypes primary intracerebral haemorrhage (PICH) and exam- (cortical, subcortical stroke). The main factors include ines what research is required. Issues related to the pre-existing high blood pressure, activation of neuroen- management of blood pressure in subarachnoid haemor- docrine systems (sympathetic, glucocorticoid, mineralo- rhage are not discussed. corticoid), increased cardiac output, the stress of hospitalization, and the Cushing reﬂex (reactive in- Blood pressure in acute stroke creases in systemic blood pressure in response to a Ischaemic stroke raised intracranial pressure) [14–17]. Because these High blood pressure is deﬁned by the World Health states provide potential targets for altering blood pres- Organization and the International Society of Hyper- sure, further research into the cause of high blood tension as a systolic blood pressure . 140 mmHg and/ pressure in acute stroke will be valuable. or a diastolic blood pressure . 90 mmHg. Observational studies suggest that approximately 75% of patients with A low–normal blood pressure is associated with severe ischaemic stroke have an elevated blood pressure when stroke (total anterior circulation syndromes)  and measured within 24–48 h of onset [6–8]. In the Inter- concurrent coronary artery events . It is likely that national Stroke Trial, a factorial trial of aspirin and some patients with low–normal blood pressure have a unfractionated heparin  involving 17 398 patients low cardiac output state secondary to heart failure and/ with ischaemic stroke, 80% of patients had high blood or acute coronary syndromes, or sepsis. pressure; the mean systolic blood pressure across the study was 160 mmHg . The natural history is for Blood pressure and outcome after stroke blood pressure to start falling within hours of stroke Several observational studies have reported on the 0263-6352 & 2003 Lippincott Williams & Wilkins DOI: 10.1097/01.hjh.0000052489.18130.43 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 666 Journal of Hypertension 2003, Vol 21 No 4 relationship between admission blood pressure and Blood pressure, cerebral perfusion, subsequent outcome in acute stroke. The interpretation autoregulation and stroke of these studies is difﬁcult because many did not Ischaemic stroke distinguish between ischaemic stroke and PICH; addi- Cerebral autoregulation normally maintains perfusion tionally, most were small and therefore could not over a wide range of systemic blood pressure. During determine whether the association was independent of the acute phase of stroke, cerebral autoregulation known prognostic factors, such as age and severity, or becomes dysfunctional  and perfusion tends to be assess effects in different subgroups of patients. Never- passively dependent on systemic pressure. Hence, it theless, a high blood pressure was usually associated has been reasoned that blood pressure should not be with an increased risk of death, or with an increased actively reduced to avoid further reducing cerebral risk of either death or dependency [17,19–25], as blood ﬂow, with the possible sequelae of infarct exten- conﬁrmed by a meta-analysis of these and other studies sion and worsening of outcome. Some studies of . calcium antagonists support this hypothesis: nicardipine reduced blood pressure and cerebral perfusion [deter- mined by single-photon emission computed tomogra- Ischaemic stroke phy (SPECT)] in parallel . However, other studies The relationship between high admission blood pres- of an angiotensin-converting enzyme (ACE) inhibitor sure and outcome (death, death or dependency) was (oral perindopril) and nitrates (intravenous sodium found in the International Stroke Trial analysis to be nitroprusside, transdermal glyceryl trinitrate) found that independent of prognostic factors, including age, gen- modest reductions in blood pressure did not apparently der, severe clinical syndrome (total anterior circulation alter cerebral blood ﬂow or middle cerebral artery blood syndrome), level of consciousness and atrial ﬁbrillation, ﬂow velocity [42–44]. Whether these latter results and the confounding factor of time to measurement indicate preserved autoregulation or simply insensitivity . Intermediate events may explain this relationship of the methods to detect small changes in cerebral because the risks of early recurrence and fatal cerebral blood ﬂow is not clear. Dysfunctional autoregulation ooedema were each positively associated with admis- does not appear to be a feature of transient ischaemic sion systolic blood pressure . However, the blood attacks . pressure at the time of these intermediate events was not recorded in this study. Haemorrhagic transforma- Cerebral perfusion might also suffer if cerebral vasodi- tion was not associated with systolic blood pressure. lators were administered in the presence of large stroke The analysis also revealed that low blood pressure, lesions causing mass effects and a rise in intracranial albeit an uncommon ﬁnding, was also independently pressure. Although no observations have been made in associated with a poor outcome , conﬁrming earlier stroke, sodium nitroprusside, a potent cerebral vasodi- studies [17,24]. The best outcome in these three stud- lator, increased intracranial pressure in patients with ies appeared to occur in patients with a high normal or vascular brain tumours, particularly when blood pres- moderately elevated systolic blood pressure. One study sure had fallen by 20% or more . reported that a reduced rate of stroke-in-progression was associated with a high blood pressure . An extrapolation of the argument that blood pressure should not be lowered is that it should be increased to Primary intracerebral haemorrhage improve perfusion. However, signiﬁcantly raising blood High admission blood pressure has been found in some pressure could promote the development of early [19,28–32], but not all [33,34], studies of PICH to be recurrence or cerebral ooedema in patients with ischae- associated with a poor outcome (increased death). Part mic stroke. of this may be explained by a positive relationship between admission blood pressure and haematoma growth, as found in three [35–37] of ﬁve studies Primary intracerebral haemorrhage [38,39], and a meta-analysis of them . This relation- The possible relationship between blood pressure and ship is confounded by the fact that both blood pressure risk of rebleeding has led inevitably to the suggestion and risk of haematoma growth are highest soon after that high blood pressure should be actively lowered. PICH. When adjusted for time after onset, no relation- One small randomized controlled trial (n ¼ 14) reported ship between admission blood pressure and haematoma that neither nicardipine (calcium antagonist) nor labeta- growth is evident [35–37]. This relationship also may lol (combined alpha- and beta-adrenergic blocker) re- reﬂect, in turn, the fact that large bleeds are more duced global or periclot cerebral blood ﬂow, measured likely to grow [33–38] and have a high blood pressure using positron emission tomography (PET), when mean secondary to the Cushing reﬂex. Unsurprisingly, hae- arterial pressure was lowered by 17% . There are no matoma growth is associated with clinical deterioration data describing the effects of actively raising blood and a poor outcome [33,35,37,38]. pressure in PICH. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Statement on blood pressure in acute stroke ISH 667 Altering blood pressure: practical Diuretics considerations A small randomized controlled trial (n ¼ 40) found that Therapy for lowering blood pressure oral bendroﬂuazide did not reduce blood pressure over A number of different drug classes may be used to the ﬁrst week after stroke , a ﬁnding which is lower blood pressure in stroke  and each has probably explained by the slow onset of action that potential advantages and disadvantages. It must be thiazide diuretics are known to have. No randomized recognized that all the data are small and inconclusive data exist for loop diuretics such as frusemide or when considering whether lowering blood pressure is bumetanide. beneﬁcial or not. Magnesium sulphate Alpha adrenergic receptor blockers Magnesium ions lower blood pressure in clinical situa- No randomized data exist for drugs such as prazosin tions with severe hypertension in the absence of stroke and doxazosin. Labetalol has been studied in a small (e.g. pre-eclampsia). A large trial is currently investigat- trial . Theoretical concerns have been raised that ing magnesium sulphate in acute stroke (Table 1). alpha blockers may inhibit or delay functional recovery . Nitric oxide donors Two small randomized controlled trials (total n ¼ 127) Angiotensin-converting enzyme (ACE) inhibitors studied transdermal glyceryl trinitrate and found that it One small randomized controlled trial (n ¼ 24) found lowered blood pressure by 6–8% without altering that oral perindopril reduced blood pressure by 11% middle cerebral artery blood ﬂow velocity or platelet without altering global cerebral blood ﬂow or middle function [44,55]. No safety issues were apparent [5,56]. cerebral blood ﬂow velocity . Intravenous sodium nitroprusside increased intracranial pressure in non-stroke patients with large mass-produ- Angiotensin receptor blockers (ARB) cing lesions, particularly when blood pressure fell by One randomized controlled trial (n ¼ 342), so far unpub- 20% or more . lished, has reported that oral candesartan reduced a composite secondary outcome (combined death, recur- Other vasodilators rent stroke or cardiac events, and dependency at 12 No randomized data exist for drugs such as hydralazine. months) by 47% in patients with severely elevated blood pressure . Unfortunately, the trial was stopped pre- Case–control studies maturely with a neutral ﬁnding for its primary outcome Several case studies have reported on the results of (total mortality and disability at 3 months). actively lowering blood pressure in acute stroke. The largest study in ischaemic stroke (n ¼ 481) used a Beta-adrenergic receptor blockers variety of drugs so class-speciﬁc interpretation of the A single trial administering oral atenolol or propranolol ﬁndings is not possible ; nevertheless, falls in blood (n ¼ 302) found a trend to a worse outcome in patients pressure of 20–30% by day 2 were associated with receiving active treatment . improved outcome and reduced cerebral ooedema. Similarly, the largest series in PICH (n ¼ 167) reported Calcium antagonists that lowering blood pressure was beneﬁcial . Other More than 25 RCTs have studied calcium antagonists and far smaller case series have found that lowering in acute stroke, mostly in patients with ischaemia. blood pressure may be detrimental [59–61]. A con- Overall, calcium antagonists did not alter functional founding factor is that blood pressure falls at varying outcome whether given intravenously or orally, or with- rates in different subjects without treatment; rapid falls in 6–12 h of stroke onset or later . One negative may in themselves be associated with an altered prog- trial found that functional outcome was worsened in nosis as found in one case series . parallel with the degree by which blood pressure fell . A small trial found that oral nicardipine reduced Therapy for raising blood pressure cerebral perfusion in parallel with its effects on blood A low or low–normal blood pressure occurs infre- pressure in patients with ischaemic stroke . By quently and may reﬂect the presence of a large contrast, another small randomized controlled trial ischaemic stroke, concurrent cardiac ischaemia or fail- reported that nicardipine did not reduce global or ure, or sepsis. Both non-pharmacological and pharmaco- periclot cerebral blood ﬂow in PICH when mean logical approaches can be used to raise blood pressure. arterial pressure was lowered by 17% . Non-pharmacological measures Centrally acting agents Blood pressure can be increased acutely but transiently No randomized data exist for drugs such as Æ–methyl- through leg-raising. Hypotension may follow dehydra- dopa, clonidine and moxonidine. tion and measures should be taken to rehydrate pa- Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 668 Journal of Hypertension 2003, Vol 21 No 4 tients with crystalloid (saline), or occasionally colloid, duced for the purposes of secondary prevention. Con- solutions . Glucose solutions should probably be tinuing therapy may deliver different potential avoided since hyperglycaemia is a risk factor for a poor problems; many patients will be taking a beta-blocker outcome . Fluid therapy can exacerbate or induce and/or calcium antagonist, classes that have, in some heart failure, a relatively common complication in trials, worsened outcome. The presence of dysphagia elderly stroke patients with comorbid heart disease. will also complicate early administration, especially for drugs administered in slow release mechanisms because Sympathomimetics these cannot be ‘crushed’ for passage down enteral Sympathomimetic drugs (e.g. adrenaline, dobutamine, feeding tubes if they are to retain their pharmacoki- dopamine, dopexamine, phenylephrine, pseudoephi- netic properties. Trial evidence is required to deter- drine) are typically used to raise blood pressure in other mine whether prior antihypertensive therapy should be areas of medicine but have potential drawbacks when continued or temporarily stopped, although it has to be used in acute stroke: they increase cardiac work and recognized that the question is complex because pa- may induce cardiac ischaemia (again, a common comor- tients will present on different combinations, formula- bid problem in stroke patients); and all tend to induce tions and doses of drugs. Secondary prevention through platelet activation. It is noteworthy that the use of such lowering blood pressure (e.g. with a diuretic and/or drugs within nasal decongestants and in weight reduc- ACE inhibitor) [71–73], will need to commence once tion programmes has been associated with the develop- the acute phase of stroke is ﬁnished and the patient is ment of stroke and other vascular disease . medically stable. Amphetamine increases blood pressure when given acutely in stroke and may improve functional outcome Blood pressure and thrombolysis . In the absence of an evidence base for managing blood pressure in acute stroke, randomized trials assessing the The apparently beneﬁcial use of vasopressors (mostly safety and efﬁcacy of alteplase (rt-PA) have developed sympathomimetics) in acute ischaemic stroke has been guidelines for managing blood pressure prior to, during described in a number of case series [66–69]. Raising a and post thrombolysis [74,75]. These state that patients normal or elevated blood pressure in acute PICH has with severe blood pressure elevation should not be not been described. given alteplase. If blood pressure rises during or immediately following treatment then the guidelines Route of administration suggest that nitrates or labetalol should be admin- Effective oral drug therapy cannot be guaranteed dur- istered. Nevertheless, these guidelines have been ques- ing the acute phase of stroke since dysphagia is present tioned in the absence of deﬁnitive data on blood in up to 50% of patients and nasogastric tube access pressure management . unreliable; insertion of tubes can be difﬁcult whilst tubes are often pulled out by confused patients. Intra- Interpretation of existing trial data venous access can provide good dose/blood pressure Several interpretations can be hypothesized from exist- titration but requires care in an Acute Stroke Unit with ing trial results, although it must be recognized that all close monitoring of blood pressure to safely administer studies to date have been small and no deﬁnitive data vasoactive drugs. Administration of drugs rectally or exist: (i) modest (5–10%) reductions in blood pressure sublingually is potentially of interest but appropriate produce minimal or no measurable changes in cerebral formulations of agents to lower or increase blood blood ﬂow. By contrast, large (. 15%) reductions in pressure do not exist. Transdermal administration blood pressure can reduce perfusion . (ii) Class- allows blood pressure response to be titrated (with speciﬁc differences may exist. In the single available removal, reduction or addition to the patch). A general trial with beta-blockers, these compounds have been comment is that it is difﬁcult to retract an oral, found to worsen outcome. Calcium antagonists are the sublingual or intramuscular dose , an important agents that have been most widely tested to date, consideration if the drug has a long duration of action unfortunately with variable results. ACE inhibitors, and the patient is unstable haemodynamically. ARB and nitrates have been tested in only a few trials, but have shown some potential for improving outcome. Continue or temporarily stop prior antihypertensive therapy Approximately 50% of patients are admitted with Current practice stroke whilst taking regular antihypertensive therapy. Current published guidelines are not based on evidence The question arises as to whether these drugs should and vary on their advice on how to manage blood be continued or temporarily stopped. If treatment is pressure in patients with acute ischaemic stroke who stopped, blood pressure falls more slowly (which might have not received thrombolytic therapy. Many give worsen outcome) and therapy will need to be reintro- absolute treatment or target levels [63,77], which may Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Statement on blood pressure in acute stroke ISH 669 be inappropriate because the effects of drugs on blood combined death or dependency) can be detected and pressure and events are proportional, not absolute. meaningful subgroup analyses performed. Smaller stud- ies are also required to assess the effect of vasoactive Although there are no data to support this view, there drugs on pathophysiological mechanisms underlying is a fairly strong consensus that blood pressure should stroke, especially cerebral perfusion [e.g. assessed using be reduced in patients with PICH to reduce the PET, xenon computed tomography (CT), CT perfusion perceived risk of haematoma growth and rebleeding. It or quantitative SPECT] and haemostasis. Several such has been suggested that patients with a severely trials have commenced or are being planned (Table 1). elevated blood pressure (. 200/120 mmHg) and PICH or coexisting critical conditions, including hypertensive Executive summary encephalopathy, aortic dissection or cardiac failure or High blood pressure (. 140/90 mmHg) is very common ischaemia, should have their blood pressure actively (approximately 75% of patients) early after ischaemic lowered . Recent guidelines have tended to empha- stroke and is independently associated with a poor size changing blood pressure by relative amounts (e.g. functional outcome. reduce blood pressure by , 20% in PICH) . High blood pressure is very common (. 80%) after Current guidelines recommend glyceryl trinitrate, so- PICH and is associated with a poor functional outcome. dium nitroprusside and labetalol as agents for lowering blood pressure, but without supportive trial data. Given Low–normal blood pressure (systolic blood pressure its pharmacological properties, sodium nitroprusside is , 120 mmHg) is uncommon (approximately 5% of pa- probably inappropriate for PICH because it is a potent tients) after acute stroke and is independently asso- antiplatelet agent and can increase intracranial pressure ciated with a poor outcome. [43,46]. Approximately 50% of patients with stroke are ad- Recommendations for future research mitted on antihypertensive therapy. There are no large completed trials which have investi- gated the safety and efﬁcacy of altering blood pressure Major uncertainty exists on the management of blood in acute ischaemic stroke or PICH . Evidence is pressure during the acute phase of both ischaemic now needed urgently that addresses the following: (i) stroke and PICH. In part, this reﬂects the need for should blood pressure be lowered in acute ischaemic pathophysiological studies to investigate the effect of stroke? This issue is important not only in its own right, altering blood pressure on cerebral blood ﬂow and but also because thrombolysis guidelines suggest that haemostasis. It also reﬂects the lack of large trials blood pressure must be controlled during treatment assessing the effect on subsequent functional outcome with alteplase. (ii) Should blood pressure be elevated in of lowering or increasing blood pressure, or of continu- acute (ischaemic) stroke, when there is evidence of ing or temporarily stopping prior antihypertensive med- hypoperfusion? (iii) Should blood pressure be lowered ication treatment. in PICH? (iv) Should prior antihypertensive therapy be continued or stopped temporarily? The optimal management of blood pressure in acute stroke remains unknown and randomized trials are Trials addressing the above questions will need to take urgently required, of sufﬁcient size and with sufﬁcient account of supplementary issues: (i) which drug class, power to take account of patient groups (age, gender, drug and formulation should be used? (ii) When should ethnicity, stroke type, stroke subtype, admission blood treatment be started (e.g. within hours or days?). (iii) pressure, presence of dysphagia), treatment paradigms How much should blood pressure be altered? (iv) What (increase or decrease blood pressure, drug class, timing, are the economic costs and beneﬁts of altering blood route of drug administration) and outcome measures pressure? (safety, functional outcome, cost–beneﬁt). These studies will need to include representative Acknowledgements groups of patients by demographic characteristics (age, The ISH Writing Group was appointed by the Interna- gender, ethnicity), blood pressure level, presence of tional Society of Hypertension and consisted of Philip pre-existing hypertension and coronary heart disease, Bath (Chairman of writing group, University of Not- stroke subtype (cortical, lacunar), severity (severe, tingham, Nottingham), John Chalmers (University of mild), and lesion size, and it is likely that responses Sydney, Sydney), William Powers (Washington Univer- may differ quantitatively between these groups of sity School of Medicine, St Louis), Lawrie Beilin patients. As a result, trials will need to be large (University of Western Australia, Perth), Stephen Davis including many thousands of patients so that modest (University of Melbourne, Melbourne), Claude Lenfant treatment effects (at least 5% absolute reduction in (National Heart Lung and Blood Institute, Bethesda, Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 670 Journal of Hypertension 2003, Vol 21 No 4 www.nottingham.ac.uk/stroke-medicine/ www.nottingham.ac.uk/stroke-medicine/ www.nottingham.ac.uk/stroke-medicine/ www.medther.gla.ac.uk/studies/images Maryland), Giuseppe Mancia (University of Milan, ACE, angiotensin-converting enzyme; CBF, cerebral blood ﬂow; IS, ischaemic stroke; mRS, modiﬁed Rankin Score; PICH, primary intracerebral haemorrhage. The IMAGES trial is primarily assessing possible neuroprotective Bicocca, Ospedale San Gerardo, Monza), Bruce Neal (University of Sydney, Sydney), Judith Whitworth email@example.com  (Australian National University, Canberra) and Alberto www.le.ac.uk/me/shg2/ Zanchetti (University of Milan, Ospedale Maggiore and COSSACShome.html Istituto Auxologico Italiano, Milan). The Writing Group enosindex.htm  Further information gratefully acknowledges the comments of the delegates at the WHO–ISH Meeting on Stroke and Blood  Pressure, held in Melbourne, December 2002. All  delegates attending the 2002 WHO–ISH Meeting on Stroke and Blood Pressure were asked to provide Starts 2003 details regarding potential conﬂicts of interest. Many Ongoing Ongoing Ongoing Ongoing Ongoing Ongoing members of the Writing Group had received research Status grants and honoraria for speaking at scientiﬁc meetings from one or more pharmaceutical companies. Death or dependency (mRS . 3) Death or dependency (mRS . 3) Death or dependency (mRS . 2) Death or dependency (global Regional CBF (xenon CT) References Primary outcome/timing outcome) at 3 months 1 Gubitz G, Sandercock P, Counsell C. Antiplatelet therapy for acute Global CBF (duplex) ischaemic stroke (Cochrane Review). The Cochrane Library, vol. 3. Oxford: Update Software; 2002. blood pressure 2 Wardlaw JM, del Zoppo G, Yamaguchi T. Thrombolysis for acute at 3 months at 2 weeks at 2 weeks ischaemic stroke (Cochrane Review). The Cochrane Library, vol. 3. Oxford: Update Software; 2002. 3 Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. The Cochrane Library, vol. 3. Oxford: Update Software; 2002. 4 Gubitz G, Counsell C, Sandercock P, Signorini D. Anticoagulants for (1) Systolic blood pressure (2) Systolic blood pressure acute ischaemic stroke (Cochrane Review). The Cochrane Library, vol. 3. Blood pressure inclusion Diastolic blood pressure Oxford: Update Software; 2002. Systolic blood pressure Systolic blood pressure Systolic blood pressure 5 Bath PMW. Optimising homeostasis. Br Med Bull 2000; 56:422–435. Ongoing or planned trials assessing the acute treatment of blood pressure in acute stroke 6 Britton M, Carlsson A, de Faire U. Blood pressure course in patients with acute stroke and matched controls. Stroke 1986; 17:861–864. 7 Morﬁs L, Schwartz RS, Poulos R, Howes LG. Blood pressure changes in 140–220 140–220 acute cerebral infarction and hemorrhage. Stroke 1997; 28:1401–1405. (mmHg) > 160 < 140 , 180 8 Osaki Y, Matsubayashi K, Yamasaki M, Okumiya K. Daily proﬁle of . 90 poststroke blood pressure change. J Stroke Cerebrovasc Dis 2000; – – 9:232–237. 9 International Stroke Trial Collaborative Group. The International Stroke Subjects Trial (IST); a randomised trial of aspirin, subcutaneous heparin, both, or 2900 5000 2700 neither among 19435 patients with acute ischaemic stroke. Lancet 1997; 24 18 24 349:1569–1581. ? 10 Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG, For the IST Collaborative Group. Blood pressure and clinical outcomes in the population International Stroke Trial. Stroke 2002; 33:1315–1320. IS (PICH) IS, PICH IS, PICH 11 Broderick J, Brott T, Barsan W, Clarke Haley E, Levy D, Marler J, et al. Target Blood pressure during the ﬁrst minutes of focal cerebral ischemia. Annal IS IS IS IS Emerg Med 1993; 22:1438–1443. 12 Lip GYH, Zariﬁs J, Farooqi IS, Page A, Sagar G, Beevers DG. Ambulatory Antihypertensives Collaborative Study Hypotension Immediately Post-Stroke blood pressure monitoring in acute stroke. The West Birmingham Stroke Intravenous Magnesium Efﬁcacy in Project. Stroke 1997; 28:31–35. Efﬁcacy of Nitric Oxide in Stroke Continue Or Stop post-Stroke 13 Jorgensen HS, Nakayama H, Christensen HR, Raaschou HO, Kampmann Control of Hypertension and JP, Olsen KS. Blood pressure in acute stroke. Cerebrovasc Dis 2002; 13:204–209. 14 Carlberg B, Asplund K, Hagg E. Factors inﬂuencing admission blood pressure levels in patients with acute stroke. Stroke 1991; 4:527–530. Stroke (IMAGES) 15 Harper G, Castleden CM, Potter JF. Factors affecting changes in blood (COSSACS) pressure after acute stroke. Stroke 1994; 25:1726–1729. (CHHIPS) 16 Treib J, Hass A, Krammer L, Stoll M, Grauer MT, Schimrigk K. Cardiac (ENOS) output in patients with acute stroke. J Neurol 1996; 243:575–578. Trial 17 Boreas AMHP, Lodder J, Kessels F, de Leeuw PW, Troost J. Predictors – Glyceryl trinitrate (transdermal) – of poststroke blood pressure level and course. J Stroke Cerebrovasc Dis 2001; 10:85–91. 18 Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classiﬁcation Dobutamine (intravenous) (2) Continue or stop prior Magnesium (intravenous) and natural history of clinically identiﬁable subtypes of cerebral infarction. antihypertensive therapy antihypertensive therapy Continue or stop prior effects of magnesium. Lancet 1991; 337:1521–1526. (1) Glyceryl trinitrate 19 Carlberg B, Asplund K, Hagg E. The prognostic value of admission Intervention (route) (2) Phenylephrine (1) ACE inhibitor blood-pressure in patients with acute stroke. Stroke 1993; 24: Losartan (oral) (transdermal) 1372–1375. 20 Leys D, Mounier-Vehier F, Mounier-Vehier C, Carre A. Relationship Table 1 between blood pressure and outcome in intracerebral haemorrhage. Stroke 1995; 26:1126–1127. 21 Armario P, Celeuela LM, Bello J, Martin-Baranera M, Hernandez Delrey R, Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Statement on blood pressure in acute stroke ISH 671 Auila A. The role of blood pressure in the prognosis of acute ischaemic changes induced by sodium nitroprusside in patients with intracranial stroke. [abstract] J Hypertens 2001; 19:513. mass lesions. J Neurosurg 1978; 48:329–331. 22 Robinson T, Waddington A, Ward-Close S, Taub N, Potter J. The 47 Powers WJ, Zazulia AR, Videen TO, Adams RE, Yundt KD, Aiyagari V, predictive role of 24-hour compared to casual blood pressure levels on et al. Autoregulation of cerebral blood ﬂow surrounding acute (6–22 h) outcome following acute stroke. Cerebrovasc Dis 1997; 7:264–272. intracerebral hemorrhage. Neurology 2001; 57:18–24. 23 Dawson SL, Manktelow BN, Robinson TG, Panerai RB, Potter JF. Which 48 The Blood Pressure in Acute Stroke Collaboration B. Vasoactive Drugs parameters of beat-to-beat blood pressure and variability best predict for Acute Stroke (Cochrane Review). The Cochrane Library. Oxford: early outcome after acute ischemic stroke? Stroke 2000; 31:463–468. Update Software; 2001. 24 Buyamba-Kabangu J, Longo-Mbenza B, Tambwe M, Dikassa L, Mbala- 49 Goldstein LB, Matchar DB, Morgenlanider JC. Drugs inﬂuence the Mukendi M. J-shaped relationship between mortality and admission blood recovery of function after stroke [abstract]. Stroke 1990; 21:179. pressure in black patients with acute stroke. J Hypertens 1995; 50 Schrader J, Luders S, Kulschewski A, Venneklass V, Berger J, Diener HC, 12:1863–1868. Dominiak P. ACCESS Study: Acute Candesartan Cilexetil Evaluation in 25 Ahmed N, Wahlgren NG. High intial blood pressure after acute stroke is Stroke Survivors. Double-blind randomised comparison of candesartan associated with poor functional outcome. J Int Med 2001; 249: cilexetil and placebo in the control of blood pressure following stroke. In: 467–473. The proceedings of the 25th Scientiﬁc Meeting of the German Hyperten- 26 Willmot M, Leonardi-Bee J, Bath PMW. High blood pressure in acute sion Society; 2001 Nov 28; Bieﬁeld, Germany. stroke and subsequent outcome: a systematic review [Abstract]. Cere- 51 Barer DH, Cruickshank JM, Ebrahim SB, Mitchell JR. Low dose beta brovasc Dis 2002; 13(suppl 3): 95. blockade in acute stroke (‘BEST’ trial): an evaluation. BMJ 1988; 27 Jorgensen H, Nakayama H, Raaschou H, Olsen T. Effect of blood 296:737–741. pressure and diabetes on stroke in progression. Lancet 1994; 344: 52 Horn J, Limburg L, Orgogozo JM. Calcium antagonists for acute ischemic 156–159. stroke (Cochrane Review). The Cochrane Library, vol. 1. Oxford: Update 28 Tuhrim S, Dambrosia J, Rice T, Mohr J, Wolf P, Heyman A, et al. Software; 2001. Prediction of intracerebral hemorrhage survival. Ann Neurol 1988; 53 Wahlgren NG, MacMahon DG, de Keyser J, Indredavik B, Ryman T, 24:258–263. INWEST Study Group. Intravenous Nimodipine West European Stroke 29 Qureshi AI, Safdar K, Weil EJ, Barch C, Bliwise DL, Colohan AR, et al. Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke. Predictors of early deterioration and mortality in black americans with Cerebrovasc Dis 1994; 4:204–210. spontaneous intracerebral hemorrhage. Stroke 1995; 26:1764–1767. 54 Author A. Bendroﬂuazide does not reduce arterial blood pressure in the 30 Dandapani BK, Suzuki S, Kelley RE, Reyes-Iglesias Y, Duncan R. Relation acute stroke period. Sixth Scientiﬁc Meeting of The Stroke Association between blood pressure and outcome in intracerebral haemorrhage. 2001; Oxford: The Stroke Association; 2001. Stroke 1995; 26:21–24. 55 Bath PMW, Pathansali R, Iddenden R, Bath FJ. The effect of transdermal 31 Terayama Y, Tanahashi N, Fukuuchi Y, Gotoh F. Prognostic value of glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet admission blood pressure in patients with intracerebral hemorrhage. Keio function in acute stroke. Cerebrovasc Dis 2001; 11:265–272. Cooperative Stroke Study. Stroke 1997; 28:1185–1188. 56 Bath PMW, Willmot M, Bath FJ. Nitric oxide donors (nitrates), L-arginine, 32 Fogelholm R, Avikainen S, Murros K. Prognostic value and determinants or nitric oxide synthase inhibitors in acute ischaemic stroke (Cochrane of ﬁrst-day mean arterial pressure in spontaneous supratentorial intracer- Review). The Cochrane Library, vol. 4. Oxford: Update Software; 2002. ebral hemorrhage. Stroke 1997; 28:1396–1400. 57 Chamorro A, Vila N, Ascaso C, Elices E, Schonewille W, Blanc R. Blood 33 Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of pressure and functional recovery in acute ischemic stroke. Stroke 1998; intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day 29:1850–1853. mortality. Stroke 1993; 24:987–993. 58 Meyer JS, Bauer RB. Medical treatment of spontaneous intracranial 34 Lisk DR, Pasteur W, Rhoades H, Putman RD, Grotta JC. Early presenta- hemorrhage by the use of hypotensive drugs. Neurology 1962; 12: tion of hemispheric intracerebral hemorrhage: Prediction of outcome and 36–47. guidelines for treatment allocation. Neurology 1994; 44:133–139. 59 Britton M, de Faire U, Helmers C. Hazards of therapy for excessive 35 Fujii Y, Tanaka R, Takeuchi S, Koike T, Minakawa T, Sasaki O. Hematoma hypertension in acute stroke. Acta Med Scand 1980; 207:253–257. enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 60 Lavin P. Management of hypertension in patients with acute stroke. Arch 1994; 80:51–57. Int Med 1986; 146:66–68. 36 Kazui S, Minematsu K, Yamamoto H, Sawada T, Yamaguchi T. Predispos- 61 Fischberg GM, Lozano E, Rajamani K, Ameriso S, Fisher MJ. Stroke ing factors to enlargement of spontaneous intracerebral hematoma. precipitated by moderate blood pressure reduction. J Emerg Med 2000; Stroke 1997; 28:2370–2375. 19:339–346. 37 Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Tanaka R. Multivariate analysis 62 Qureshi AI, Bliwise DL, Bliwise NG, Akbar MS, Uzen G, Frankel MR. Rate of predictors of hematoma enlargement in spontaneous intracerebral of 24-hour blood pressure decline and mortality after spontaneous hemorrhage. Stroke 1998; 29:1160–1166. intracerebral hemorrhage: a retrospective analysis with a random effects 38 Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, et al. regression model. Crit Care Med 1999; 27:480–485. Early hemorrhage growth in patients with intracerebral hemorrhage. 63 Adams HP, Brott TG, Crowell RM, Furlan AJ, Gomex CR, Grotta J, et al. Stroke 1997; 28:1–5. Guidelines for the management of patients with acute ischemic stroke. A 39 Jauch E, Barsan W, Khoury J, Brott T, Pancioli A, Kothari Rea. An analysis statement for healthcare professionals from a special writing group of the of factors associated with early intracerebral hemorrhage (ICH) growth. Stroke Council, American Heart Association. Stroke 1994; 25:1901– Stroke 2001; 32:338. 1914. 40 Meyer JS, Shimazu K, Fukuuchi Y, Ohuchi T, Okamoto S, Koto A, et al. 64 Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, Impaired neurogenic cerebrovascular control and dysautoregulation after et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J stroke. Stroke 1973; 4:169–186. Med 2000; 343:1826–1832. 41 Lisk DR, Grotta JC, Lamki LM, Tran HD, Taylor JW, Molony DA, et al. 65 Martinsson L, Wahlgren NG. Dexamphetamine treatment increases blood Should hypertension be treated after acute stroke. A randomised pressure and heart rate but not body temperature in acute cerebral controlled trial using single photon emission computed tomography. Arch ischaemia [Abstract]. Cerebrovasc Dis 2002; 13(suppl 3):63. Neurol 1993; 50:855–862. 66 Farhat SM, Schneider RC, 1825. Observations on the effect of systemic 42 Dyker AG, Grosset DG, Lees K. Perindopril reduces blood pressure but blood prssure on intracranial circulation in patients with cerebrovascular not cerebral blood ﬂow in patients with recent cerebral ischemic stroke. insufﬁciency. J Neurol 1967; 27:441–445. Stroke 1997; 28:580–583. 67 Wise GR. Vasopressor-drug therapy for complications of cerebral 43 Butterworth RJ, Cluckie A, Jackson SHD, Buxton-Thomas M, Bath PMW. arteriography. N Engl J Med 1970; 282:610–613. Pathophysiological assessment of nitric oxide (given as sodium nitroprus- 68 Wise G, Sutter R, Burkholder J. The treatment of brain ischaemia with side) in acute ischaemic stroke. Cerebrovasc Dis 1998; 8:158–165. vasopressor drug. Stroke 1972; 3:135–140. 44 Rashid P, Leonardi-Bee JA, Weaver CS, Bath FJ, Bath PMW. The effect 69 Rordorf G, Cramer SC, Eﬁrd JT, Schwamm LH, Buonanno F, Koroshetz of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure WJ. Pharmacological elevation of blood pressure in acute stroke. Clinical and middle cerebral artery blood velocity in acute stroke [Abstract]. effects and safety. Stroke 1997; 28:2133–2138. Stroke 2002; 33:383. 70 Spence JD. Hypertension and stroke. Can J Neurol Sci 2002; 29: 45 Skinhoj E, Rasmussen-Hoedt K, Paulson OB, Lassen NA, 1824. Regional 113–114. cerebral blood ﬂow and its autoregulation in patients with transient focal 71 PATS Collaborating Group. Post-stroke antihypertensive treatment study. cerebral ischemic attacks. Neurology 1970; 20:485–493. A preliminary result. Chin Med J 1995; 108:710–717. 46 Cottrell JE, Patel K, Turndorf H, Ransohoff J. Intracranial pressure 72 The Heart Outcome Prevention Evaluation Study Investigators. Effects of Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 672 Journal of Hypertension 2003, Vol 21 No 4 an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342:145–153. 73 PROGRESS Collaborative Group. Randomised trial of a perindopril- based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–1041. 74 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute stroke. N Engl J Med 1995; 333:1581–1587. 75 Brott T, Lu M, Kothari R, Fagan SC, Frankel M, Grotta JC, et al. Hypertension and its treatment in the NINDS rt-PA stroke trial. Stroke 1998; 29:1504–1509. 76 Slyter H. Ethical challenges in stroke research. Stroke 1998; 29: 1725–1729. 77 The European Ad Hoc Consensus Group. European strategies for early intervention in stroke. Cerebrovasc Dis 1996; 6:315–324. 78 O’Connell JE, Gray GS. Treating hypertension after stroke. BMJ 1994; 308:1523–1524. 79 Morgenstern LB. Lowering blood pressure in acute intracerebral hemor- rhage. Safe, but will it help? Neurology 2001; 57:5–6. 80 Blood pressure in Acute Stroke Collaboration (BASC). Interventions for deliberately altering blood pressure in acute stroke (Cochrane Review). The Cochrane Library, vol. 4. Oxford: Update Software; 2001. 81 Bath PM. Major Ongoing Stroke Trials. Efﬁcacy of Nitric Oxide in Stroke (ENOS) Trial [Abstract]. Stroke 2001; 32:2450–2451. 82 Lees KR. Effect of losartan on blood pressure, cerebral perfusion and renal function in patients following acute stroke (6 June 2000). National Research Register, 3 edn. Leeds: National Research Register; 2000. 83 Images Trial Group. IMAGES – intravenous magnesium in acute stroke [abstract]. Stroke 1990; 30:268. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.