International Society of Hypertension (ISH)

					                                                                                                                  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 [11] 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 [10].
 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 [4]. 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 [5]. 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) [18] and
 measured within 24–48 h of onset [6–8]. In the Inter-      concurrent coronary artery events [10]. It is likely that
 national Stroke Trial, a factorial trial of aspirin and    some patients with low–normal blood pressure have a
 unfractionated heparin [9] 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 [10]. 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 [40] 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
[26].                                                       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 [41]. 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
[10]. 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 [10]. However, the blood
                                                            attacks [45].
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 [10], 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 [46].
reported that a reduced rate of stroke-in-progression
was associated with a high blood pressure [27].
                                                            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 [26]. 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% [47]. 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.


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                                                                         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 [54], a finding which is
 lower blood pressure in stroke [48] 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 [47]. Theoretical concerns have been raised that      ing magnesium sulphate in acute stroke (Table 1).
 alpha blockers may inhibit or delay functional recovery
 [49].                                                       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 [42].                           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 [46].
 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 [50]. 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 [57]; 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 [51].                            improved outcome and reduced cerebral ooedema.
                                                             Similarly, the largest series in PICH (n ¼ 167) reported
 Calcium antagonists                                         that lowering blood pressure was beneficial [58]. 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 [52]. 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 [62].
 parallel with the degree by which blood pressure fell
 [53]. 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 [41]. 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% [47].
                                                             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 [63]. 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 [5]. 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 [65].              medically stable.
Amphetamine increases blood pressure when given
acutely in stroke and may improve functional outcome         Blood pressure and thrombolysis
[65].                                                        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 [76].
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 [41]. (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 [70], 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 [78]. 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) [79].
                                                              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 [80]. 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




                                                                                                                                                                                                                                                                                                                              k.r.lees@clinmed.gla.ac.uk [82]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 (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 [81]
                                                                                                          Further information




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 gratefully acknowledges the comments of the delegates
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 at the WHO–ISH Meeting on Stroke and Blood
                                                                                                                                                                                                   [80]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Pressure, held in Melbourne, December 2002. All




                                                                                                                                                                                                                                                                                                                                                                [83]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 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

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                                                                                                                                                                                                                                                                                      Ongoing

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                                                                                                                                                                                                                                                                                                                                                                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



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                                                                                                                                                                                                                                                                                      Diastolic blood pressure




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Oxford: Update Software; 2002.
                                                                                                                                                                   Systolic blood pressure

                                                                                                                                                                   Systolic blood pressure



                                                                                                                                                                                                                                                                                      Systolic blood pressure




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                                                                                             (mmHg)




                                                                                                                                                                   > 160

                                                                                                                                                                   < 140

                                                                                                                                                                   , 180




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  8   Osaki Y, Matsubayashi K, Yamasaki M, Okumiya K. Daily profile of
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                                                                                                                                                                                                                                                                                      –




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                                                                                                          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
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                                                                                                                                                                         IS, PICH




                                                                                                                                                                                                                              IS, PICH




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                                                                                                                                                                         IS



                                                                                                                                                                                                   IS




                                                                                                                                                                                                                                                                                      IS

                                                                                                                                                                                                                                                                                                                              IS




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                                                                                                                                   Continue Or Stop post-Stroke




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                                                                                                                                                                                                                              Glyceryl trinitrate (transdermal) –




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                                                                                                                                                                                                                              (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.
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                                                                                                          Intervention (route)




                                                                                                                                                                   (2) Phenylephrine
                                                                                                                                                                   (1) ACE inhibitor




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      blood-pressure in patients with acute stroke. Stroke 1993; 24:
                                                                                                                                                                                                                                                                                                                              Losartan (oral)
                                                                                                                                                                                                                              (transdermal)




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      1372–1375.
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          Table 1




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      between blood pressure and outcome in intracerebral haemorrhage.
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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 21   Armario P, Celeuela LM, Bello J, Martin-Baranera M, Hernandez Delrey R,




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