High blood pressure (BP) is present in 80% of patients with acute ischaemic stroke and is independently associated with poor outcome. Although this epidemiology suggests that BP should be lowered acutely, concerns about dysfunctional cerebral autoregulation suggest otherwise. Several small randomised trials have assessed cerebral blood flow with various antihypertensive classes and agents in acute ischaemic stroke. Overall, these studies showed no change in cerebral perfusion, although the numbers of studies and patients are limited and there are methodological problems with some trials. There are no large published randomised trials assessing outcome with BP lowering in acute stroke. Calcium channel blockers did not alter outcome after ischaemic stroke (29 trials, 7,665 patients). However, some trials, especially those testing intravenous calcium channel blockers (INWEST) or oral β-receptor antagonists (BEST) reported real or potential hazard. In contrast, oral candesartan reduced combined vascular events in 339 patients with ischaemic stroke (ACCESS) although it had no effect on disability. The CHHIPS trial found that death was reduced in patients randomised to active treatment (labetalol, lisinopril) as compared with placebo. Two larger trials reported that glucose-potassium-insulin therapy (GIST) or magnesium (IMAGES) lowered BP but had no effect on functional outcome. The INTERACT pilot trial studied patients with intracerebral haemorrhage and found that an intensive BP-lowering regime non-significantly reduced haematoma expansion. There are four large ongoing trials examining whether to continue or stop pre-stroke antihypertensive therapy (COSSACS, ENOS) or lower BP in acute stroke (ENOS, SCAST) or haemorrhage (INTERACT 2).

1.
Wallace JD, Levy LL: Blood pressure after stroke. JAMA 1981;246:2177–2180.
2.
Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG, for the IST Collaborative Group: Blood pressure and clinical outcomes in the International Stroke Trial. Stroke 2002;33:1315–1320.
3.
Carlberg B, Asplund K, Hagg E: Factors influencing admission blood pressure levels in patients with acute stroke. Stroke 1991;4:527–530.
4.
Britton M, Carlsson A, de Faire U: Blood pressure course in patients with acute stroke and matched controls. Stroke 1986;17:861–864.
5.
Willmot M, Leonardi-Bee J, Bath PM: High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension 2004;43:18–24.
6.
Sprigg N, Gray LJ, Bath PMW, Boysen G, De Deyn PP, Friis P, Leys D, Marttila R, Olsson J-E, O’Neill D, Ringlestein B, van der Sande J-J, Lindenstrom E, TAIST Investigators: Relationship between outcome and baseline blood pressure and other haemodynamic measures in acute ischaemic stroke: data from the TAIST trial. J Hypertens 2006;24:1413–1417.
7.
Bowes MP, Zivin JA, Thomas GR, Thibodeaux H, Fagan SC: Acute hypertension, but not thrombolysis, increases the incidence and severity of hemorrhagic transformation following experimental stroke in rabbits. Exp Neurol 1996;141:40–46.
8.
Saku Y, Choki J, Waki R, Masuda J, Tamaki K, Fujishima M, Ogata J: Hemorrhagic infarct induced by arterial hypertension in cat brain following middle cerebral artery occlusion. Stroke 1990;21:589–595.
9.
Sare GM, Gray LJ, England T, Geeganage CM, Bath PMW: The relationship between baseline blood pressure and CT findings in acute stroke: data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’ (abstract). Stroke 2008;39:610.
10.
Meyer JS, Shimazu K, Fukuuchi Y, Ohuchi T, Okamoto S, Koto A, Ericsson AD: Impaired neurogenic cerebrovascular control and dysautoregulation after stroke. Stroke 1973;4:169–186.
11.
Hachinski V: Hypertension in acute ischaemic strokes. Arch Neurol 1985;42:1002.
12.
Sare GM, Gray LJ, Bath PMW: Effect of antihypertensive agents on cerebral blood flow and cerebral blood flow velocity in acute ischaemic stroke – systematic review of controlled studies. J Hypertens 2008;26:1058–1064.
13.
Hakim AM, Evans AC, Berger L, Kuwabara H, Worsley K, Marchal G, Biel C, Pokrupa R, Diksic M, Meyer E, et al: The effect of nimodipine on the evolution of human cerebral infarction studied by PET. J Cereb Blood Flow Metab 1989;9:523–534.
14.
Lisk D, Grotta J, Lamki L, et al: Should hypertension be treated after acute stroke? A randomised controlled trial using single photon emission computed tomography. Arch Neurol 1993;50:855–862.
15.
Dyker AG, Grosset DG, Lees K: Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke. Stroke 1997;28:580–583.
16.
Infield B, Davis SM, Donnan GA, Yasaka M, Lichtenstein M, Mitchell PJ, Fitt GJ: Nimodipine and perfusion changes after stroke. Stroke 1999;30:1417–1423.
17.
Nazir FS, Overell JR, Bolster A, Hilditch TE, Reid JL, Lees KR: The effect of losartan on global and focal cerebral perfusion and on renal function in hypertensives in mild early ischaemic stroke. J Hypertens 2004;22:989–995.
18.
Nazir FS, Overell JR, Bolster A, Hilditch TE, Lees KR: Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial. Cerebrovasc Dis 2005;19:77–83.
19.
Willmot M, Ghadami A, Whysall B, Clarke W, Wardlaw J, Bath PM: Transdermal glyceryl trinitrate lowers blood pressure and maintains cerebral blood flow in recent stroke. Hypertension 2006;47:1209–1215.
20.
Eveson DJ, Robinson TG, Potter JF: Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up. Am J Hypertens 2007;20:270–277.
21.
Potter J, for the CHHIPS Trialists: Control of hypertension and hypotension immediately post-stroke (CHHIPS) pilot study; in Am Stroke Assoc Int Stroke Conf, February 2008, New Orleans.
22.
Nazir FS, Overell JR, Hilditch TE, Lees KR: The effect of losartan on global and focal cerebral perfusion and renal function in hypertensives in early ischaemic stroke (abstract). Cerebrovasc Dis 2003;16(suppl 4):31.
23.
Schrader J, Luders S, Kulchewski A, Berger J, Zidek W, Treib J, Einhaupl K, Diener H-C, Dominiak P: The ACCESS Study. Evaluation of acute candesartan therapy in stroke survivors. Stroke 2003;34:1699–1703.
24.
Diener H-C, Sacco RL, Yusuf S; for the Steering Committee and PRoFESS Study Group: Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the prevention regimen for effectively avoiding second strokes trial (PRoFESS). Cerebrovasc Dis 2007;23:368–380.
25.
Barer DH, Cruickshank JM, Ebrahim SB, Mitchell JR: Low dose beta blockade in acute stroke (‘BEST’ trial): an evaluation. BMJ 1988;296:737–741.
26.
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.
27.
Brott T, Lu M, Kothari R, Fagan SC, Frankel M, Grotta JC, Broderick J, Kwiatkowski T, Lewandowski C, Haley E, Marler J, Tilley B, The NINDS rt-PA Stroke Study Group: Hypertension and its treatment in the NINDS rt-PA stroke trial. Stroke 1998;29:1504–1509.
28.
Horn J, Limburg M: Calcium antagonists for acute ischaemic stroke. Cochrane Database Syst Rev 2000;CD001928.
29.
Blood pressure in Acute Stroke Collaboration: The effect of vasoactive drugs on blood pressure and outcome in acute stroke. Cochrane Database Syst Rev 2001; CD000039.
30.
Wahlgren NG, MacMahon DG, de Keyser J, Indredavik B, Ryman T, INWEST Study Group: Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis 1994;4:204–210.
31.
Ahmed N, Nasman P, Wahlgren NG: Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke 2000;31:1250–1255.
32.
Bridgers SL, Koch G, Munera C, Karwon M, Kurtz NM: Intravenous nimodipine in acute stroke: interim analysis of randomized trials (abstract). Stroke 1991;22:153.
33.
Eames PJ, Robinson TG, Panerai RB, Potter JF: Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post stroke period. Cerebrovasc Dis 2005;19:253–259.
34.
Eames JP, Robinson TG, Panerai RB, Potter J: The systemic haemodynamic and cerebral autoregulatory effects of bendrofluazide in the subacute post-stroke period. J Hypertens 2004;22:2017–2024.
35.
Bath PMW, Pathansali R, Iddenden R, Bath FJ: The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke. Cerebrovasc Dis 2001;11:265–272.
36.
Rashid P, Weaver C, Leonardi-Bee JA, Fletcher S, Bath FJ, Bath PMW: The effects of transdermal glyceryl trinitrate, a nitric oxide donor on blood pressure, cerebral and cardiac haemodynamics and plasma nitric oxide levels in acute stroke. J Stroke Cerebrovasc Dis 2003;13:143–151.
37.
Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators: Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439.
38.
Scott JF, Robinson GM, French JM, O’Connell JE, Alberti KG, Gray CS: Blood pressure response to glucose potassium insulin therapy in patients with acute stroke with mild to moderate hyperglycaemia. J Neurol Neurosurg Psychiatry 2001;70:401–404.
39.
Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF, Alberti KG, Gist Trialists Collaboration: Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 2007;6:397–406.
40.
Geeganage C, Sare GM, Bath PM: Pulse pressure as a predictor of stroke. Expert Rev Neurother 2008;8:165–167.
41.
Eveson DJ, Robinson TG, Potter JF: Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up. Am J Hypertens 2007;20:270–277.
42.
Willmot M, Ghadami A, Gray LJ, Bath PMW: The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on systemic haemodynamics and cerebral perfusion in acute stroke. J Hum Hypertens 2006;19:824–847.
43.
Gray LJ, Sprigg N, Rashid PA, Willmot M, Bath PMW: Effect of nitric oxide donors on blood pressure and pulse pressure in acute and sub-actue stroke. J Stroke Cerebrovasc Dis 2006;15:245–249.
44.
Nyrop M, Zweifler AJ: Platelet aggregation in hypertension and the effects of antihypertensive treatment. J Hypertens 1988;6:263–266.
45.
Butterworth RJ, Cluckie A, Jackson SHD, Buxton-Thomas M, Bath PMW: Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischaemic stroke. Cerebrovasc Dis 1998;8:158–165.
46.
Horn J, deHaan R, Vermeulen M, Luiten PGM, Limburg M: Nimodipine in animal model experiments of focal cerebral ischemia. Stroke 2001;32:2433–2438.
47.
Willmot M, Murphy S, Leonardi-Bee J, Bath P: Systematic review of nitric oxide donors and L-arginine in experimental stroke: effects on infarct size and cerebral blood flow (abstract). Cerebrovasc Dis 2003;16:S366.
48.
Lu Q, Zhu YZ, Wong PT: Angiotensin receptor gene expression in candesartan mediated neuroprotection. Neuroreport 2004;15:2643–2646.
49.
Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng P, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang DJ, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J, for the INTERACT Investigators: Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008;7:391–399.
50.
The European Stroke Association (ESO) Executive Committee and the ESO Writing Committee: Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008;25:457–507.
51.
The ENOS Trial Investigators: Glyceryl trinitrate vs. control, and continuing vs. stopping temporarily prior antihypertensive therapy, in acute stroke: rationale and design of the Efficacy of Nitric Oxide in Stroke (ENOS) trial (ISRCTN99414122). Int J Stroke 2006;1:245–249.
52.
COSSACS Trial Group: COSSACS (Continue or Stop post-Stroke Antihypertensives Collaborative Study): rationale and design. J Hypertens 2005;23:455–458.
53.
Rashid P, Leonardi-Bee J, Bath P: Blood pressure reduction and the secondary prevention of stroke and other vascular events: a systematic review. Stroke 2003;34:2741–2749.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.