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(Stroke. 2001;32:1697-a.)
© 2001 American Heart Association, Inc.

Letters to the Editor

Hypertension in Acute Stroke: What to Do?

Philip Bath, FRCP

Division of Stroke Medicine, University of Nottingham, Nottingham, UK

Gudren Boysen, MD

Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark

Geoff Donnan, MD

National Stroke Research Institute, Heidelberg, Australia

Markku Kaste, MD

Department of Neurology, University of Helsinki, Helsinki, Finland

Kennedy R Lees, FRCP

Acute Stroke Unit, Western Infirmary, Glasgow, UK

Tom Olsen, MD

Department of Neurology, Gentofte University Hospital, Hellerup, Denmark

Karsten Overgaard, MD

The Copenhagen Stroke Unit, Frederiksberg Hospital, Copenhagen, Denmark

Peter Sandercock, FRCP

Department of Clinical Neurosciences, Western General Hospitals, Edinburgh, UK

Nils-Gunnar Wahlgren, MD

Department of Neurology, Karolinska Hospital, Stockholm, Sweden

To the Editor:

Hypertension is common during the acute phase of stroke, and its management remains controversial. To explore this issue further, we held an ad hoc workshop at the World Stroke Conference, Melbourne, November 2000, and report here its discussion and conclusions.

Hypertension is common (>50%) in both ischemic and hemorrhagic stroke, although its incidence depends on definitions and when and how blood pressure (BP) measurements are made. Hypertension is associated with a poor outcome,¹ a relationship which is probably independent of stroke severity or clinical subtype. The cause of the negative relationship between BP and outcome is unclear but may relate to the development of reinfarction, cerebral edema, or hemorrhagic transformation.

Our workshop agreed that trials are needed to test whether BP should be lowered in subjects with acute primary intracerebral hemorrhage. In contrast, significant differences of opinion existed on whether BP should be elevated or reduced in acute ischemic stroke. Existing data do not provide an answer: trials of beta receptor antagonists (ß-RA) and some calcium channel blockers (CCB)—in which BP lowering occurred—and diaspirin cross-linked hemoglobin (which increases BP) were all complicated by worsened outcome in the treatment group.^{2 3 4 5 6 7} It is unlikely that a single mechanism explains these findings, but CCB can reduce cerebral perfusion.^{8 9} We did not feel that the BP management strategy utilized in the NINDS and ECASS II thrombolysis trials^{10 11} helped in deciding how to manage BP in general, because patients not treated with thrombolytics are a different population with a different natural history.

A question that we could not answer was that of what agent should be used to alter BP, although the group agreed that differences between drug classes might be important and that extrapolating the findings of one class (eg, CCB) to other classes was inappropriate. Excluding ß-RA and CCB (in which the existing data are not encouraging), small studies of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, and nitric oxide donors have been completed or are underway.^{12 13 14 15 16} These agents are multimodal in their action, thereby increasing the likelihood that efficacy trials might be positive; eg, angiotensin receptor antagonists will counteract the effects of activation of the renin-angiotensin system, nitrates will replace low vascular nitric oxide levels,¹⁷ and both are neuroprotective in experimental stroke. A phase II clinical trial of elevating BP (with dobutamine) is also underway in ischemic stroke.¹⁶ The group felt that any efficacy trial aiming to change BP would need to be of sufficient size to assess effects in subgroups, including subjects with or without prior hypertension and patients with different subtypes of stroke (eg, lacunar or cortical infarction).

The method of delivery for any intervention was also discussed. We felt that intravenous formulations were not necessarily ideal because they would increase monitoring requirements, would be more susceptible to causing sudden or extreme changes in BP, and might delay or limit early mobilization and rehabilitation. Attractive routes of delivery included oral "melt" and transdermal preparations, both of which avoid problems with dysphagia, a common complication of acute stroke.

Although we discussed when treatment should commence after stroke, current information does not give any guidance; trials of changing BP should factor this question into their design and analyses. We felt that treatment should continue for a week or so, a time period over which hypertension will settle in most patients and after which most clinicians are comfortable about initiating routine treatment.

Although the ultimate question is to determine the effect of changing BP on functional outcome, studies are also required to assess the effect of vasoactive drugs on cerebral perfusion. Very few studies have been performed,¹⁸ and further (semi-)quantitative assessment is urgently required, eg, with positron emission tomography, single-photon emission CT, transcranial Doppler, MR perfusion and diffusion (with assessment of mismatch), quantitative CT perfusion, or xenon CT scanning. A further critical question is whether prior antihypertensive medication should be continued or stopped, since current practice varies.¹⁹ Once again, no randomized trial data exist, and it is vital that this question is examined, either as part of a BP modulation trial or separately.

Workshop attendees are involved with ongoing trials,¹⁶ and we plan to meet again.

References

1. Warlow CP, Dennis MS, van Gijn J, Hankey GJ, Sandercock PAG, Bamford JM, Wardlaw J. Stroke: A Practical Guide to Management. Oxford, UK: Blackwell Science; 1996.
2. Barer DH, Cruickshank JM, Ebrahim SB, Mitchell JR. Low dose beta blockade in acute stroke ("BEST" trial): an evaluation. BMJ. 1988;296:737–741.
3. Bridgers SL, Koch G, Munera C, Karwon M, Kurtz NM. Intravenous nimodipine in acute stroke: interim analysis of randomized trials. Stroke. 1991;22:153. Abstract.
4. Wahlgren NG, MacMahon DG, de Keyser J, Indredavik B, Ryman T, for the 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.
5. Kaste M, Fogelholm R, Erilä T, Palomaki H, Murros K, Rissanen A, Sarna S. A randomized, double-blind placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke. Stroke. 1994;25:1348–1353.[Abstract]
6. Squire IB, Lees KR, Pryse-Phillips W, Kertesz A, Bamford J. The effects of lifarizine in acute cerebral infarction: a pilot study. Cerebrovasc Dis. 1996;6:156–160.
7. Saxena R, Wijnhoud AD, Carton H, Hacke W, Kaste M, Przybelski RJ, Stern KN, Koudstaal PJ. Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke. 1999;30:993–996.[Abstract/Free Full Text]
8. Vorstrup S, Andersen A, Blegvad N, Paulson OB. Calcium antagonist (PY 108–068) treatment may further decrease flow in ischaemic areas in acute stroke. J Cereb Blood Flow Metab. 1986;6:222–229.[Medline] [Order article via Infotrieve]
9. Lisk DR, Grotta JC, Lamki LM, Tran HD, Taylor JW, Molony DA, Barron BJ. Should hypertension be treated after acute stroke? A randomised controlled trial using single photon emission computed tomography. Arch Neurol. 1993;50:855–862.[Abstract]
10. Brott T, Lu M, Kothari R, Fagan SC, Frankel M, Grotta JC, Broderick J, Kwiatkowski T, Lewandowski C, Haley EC, Marler JR, Tilley BC, for the NINDS rt-PA Stroke Study Group. Hypertension and its treatment in the NINDS rt-PA stroke trial. Stroke. 1998;29:1504–1509.[Abstract/Free Full Text]
11. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P, for the Second European-Australasian Acute Stroke Study Investigators. Randomized double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998;352:1245–1251.[Medline] [Order article via Infotrieve]
12. Waldemar G, Vorstrup S, Andersen A, Pedersen H, Paulson OB. Angiotensin converting enzyme inhibition and regional cerebral blood flow in acute stroke. J Cardiovasc Pharmacol. 1989;14:722–729.[Medline] [Order article via Infotrieve]
13. 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.[Abstract/Free Full Text]
14. Lees KR. Effect of losartan on blood pressure, cerebral perfusion and renal function in patients following acute stroke. In: National Research Register. Leeds, UK: National Research Register; 2000.
15. 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. In press.
16. Blood Pressure in Acute Stroke Collaboration (BASC). Interventions for deliberately altering blood pressure in acute stroke (Cochrane review). In: The Cochrane Library, issue 2, 2001. Oxford, UK: Update Software.
17. Rashid P, Bath P. Plasma nitric oxide (nitrate) in stroke by type, severity and outcome. Stroke. 2000;31:532. Abstract.
18. Mazumdar R, Bath F, Bath P. Vasoactive drugs on cerebral blood flow in acute ischaemic stroke. Stroke. 2000;31:135. Abstract.
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