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The management of blood pressure in acute stroke
Reflection & Reaction The management of blood pressure in acute stroke Physicians who care for patients in the acute phase of stroke face a major dilemma with regard to bloodpressure management: there is a lack of adequate evidence to guide their decisions, as reviewed in a recent statement from the International Society of Hypertension.1 This lack of evidence is exacerbated by the well-documented changes in blood pressure that occur in the first few days after stroke onset; high blood pressure is reported in the first 24–48 h in about 80% of patients, which subsides over the next few days or weeks.1 Decisions are also compounded by the differences in pathophysiology and clinical course of acute ischaemic stroke compared with primary intracerebral haemorrhage; blood pressure tends to be highest and prognosis worst in the latter. In the absence of reliable evidence and in an acute and commonly fatal clinical situation, it is not surprising that there are strong diverging opinions on what to do about blood pressure. These include the giving of bloodpressure lowering drugs, the stopping of existing blood-pressure lowering treatment, or the raising of blood pressure.1 Those who advocate lowering of blood pressure are influenced mainly by the evidence that blood-pressure lowering is the most effective strategy for both the primary prevention of stroke2,3 and for the prevention of recurrent stroke in patients with cerebrovascular disease.2–4 Those who advocate suspension of antihypertensive drugs and recommend the raising of blood pressure are concerned that further reductions in cerebral perfusion will exacerbate cerebral ischaemia.1 The Acute Candesartan Citexetil Therapy in Stroke Survivors (ACCESS) study makes a useful contribution to this debate.5 This randomised, double-blind, placebocontrolled study was designed to test the safety of moderate blood-pressure reduction by giving candesartan to 500 patients with hypertension (blood pressure >180–200/105–110 mm Hg) in the first 36 h after acute ischaemic stroke. The controlled phase, which
compared candesartan (4–16 mg) with placebo, lasted for 7 days.5 The trial was stopped prematurely because of a significant reduction (48%) in the secondary endpoint (combined death, recurrent stroke, cardiac events, and dependency at 12 months [odds ratio=0·48; 95% CI 0·25–0·89]), by which time 342 patients had been randomly assigned. Unfortunately, the primary end-point (death and disability at 3 months) was unchanged. The absence of any adverse cerebral (or cardiac) events related to bloodpressure reduction in the active treatment group is particularly important in relation to safety. There have been many other small but inconclusive trials of bloodpressure lowering in the acute phase of stroke. These trials have used various drugs, such as the calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, diuretics, beta blockers, and nitrates.1 Some case-control studies have reported that blood-pressure lowering is beneficial in both acute ischaemic stroke and in primary intracerebral haemorrhage, whereas others have reported detrimental outcomes.1 However, these observational studies are subject to chance and bias, due partly to the variation in stroke subtype, stroke severity, the time since stroke onset, diagnostic rigour, route of administration of bloodpressure lowering drugs, and the algorithms used to control blood pressure.1 These issues can only be resolved by well-designed, large-scale, randomised trials, as suggested by the recent statement from the International Society of Hypertension.1 We also need pathophysiological studies to investigate the effects of blood-pressure alteration on cerebral blood flow and haemostasis in different stroke types and clinical situations. In addition, we need outcome studies to address many questions. For example, should blood pressure be lowered in acute ischaemic stroke and if so, to what extent? Should blood pressure be lowered in primary intracerebral haemorrhage and if so, to what extent? Should blood pressure be raised when there is evidence of hypoperfusion?
THE LANCET Neurology Vol 2 October 2003
http://neurology.thelancet.com
And should prior antihypertensive treatment be continued or stopped temporarily? Given the many types of stroke, and the wide range of blood pressures in patients with acute stroke, it may be wise to start by investigating the effects of blood-pressure lowering in hypertensive patients with primary intracerebral haemorrhage, in whom the association between blood pressure and the risk of stroke is strong. A positive result would provide a strong rationale for further studies on bloodpressure lowering in patients with hypertension and acute ischaemic stroke and in normotensive patients with primary intracerebral haemorrhage. Additional issues include the time window for initiation of treatment, target blood pressure, and the route of drug administration, particularly in patients with severe stroke and impaired consciousness. In the meantime, the ACCESS study should reassure investigators who are keen to examine these issues that careful studies are safe for the participants and that the potential gains in terms of lives saved and disability averted are substantial.5 John Chalmers Institute for International Health, University of Sydney (C37), 144-46 Burren Street, Sydney, NSW 2042, Australia. Email [email protected] Conflict of interest
JC was co-principal investigator for the Perindopril Protection Against Recurrent Stroke Study and an author of the International Society of Hypertension Statements on the management of blood pressure in acute stroke and on blood pressure lowering and stroke prevention. References 1 2 3
4
5
Bath P, Chalmers J, Powers W, et al. Statement on the management of blood pressure in acute stroke. J Hypertens 2003; 21: 665–72. Chalmers J, Todd A, Chapman N, et al. Statement on blood pressure lowering and stroke prevention. J Hypertens 2003; 21: 651–63. Chobanian AV, Bakris GL, Black HL, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003; 289: 2560–71. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure lowering regimen among 6105 patients with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41. Schrader J, Lüders S, Kulschewski A, et. al. The ACCESS Study: Evaluation of acute condensation cilexetil therapy in stroke survivors. Stroke 2003; 34: 1699–1703.
For personal use. Only reproduce with permission from The Lancet.
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compared candesartan (4–16 mg) with placebo, lasted for 7 days.5 The trial was stopped prematurely because of a significant reduction (48%) in the secondary endpoint (combined death, recurrent stroke, cardiac events, and dependency at 12 months [odds ratio=0·48; 95% CI 0·25–0·89]), by which time 342 patients had been randomly assigned. Unfortunately, the primary end-point (death and disability at 3 months) was unchanged. The absence of any adverse cerebral (or cardiac) events related to bloodpressure reduction in the active treatment group is particularly important in relation to safety. There have been many other small but inconclusive trials of bloodpressure lowering in the acute phase of stroke. These trials have used various drugs, such as the calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, diuretics, beta blockers, and nitrates.1 Some case-control studies have reported that blood-pressure lowering is beneficial in both acute ischaemic stroke and in primary intracerebral haemorrhage, whereas others have reported detrimental outcomes.1 However, these observational studies are subject to chance and bias, due partly to the variation in stroke subtype, stroke severity, the time since stroke onset, diagnostic rigour, route of administration of bloodpressure lowering drugs, and the algorithms used to control blood pressure.1 These issues can only be resolved by well-designed, large-scale, randomised trials, as suggested by the recent statement from the International Society of Hypertension.1 We also need pathophysiological studies to investigate the effects of blood-pressure alteration on cerebral blood flow and haemostasis in different stroke types and clinical situations. In addition, we need outcome studies to address many questions. For example, should blood pressure be lowered in acute ischaemic stroke and if so, to what extent? Should blood pressure be lowered in primary intracerebral haemorrhage and if so, to what extent? Should blood pressure be raised when there is evidence of hypoperfusion?
THE LANCET Neurology Vol 2 October 2003
http://neurology.thelancet.com
And should prior antihypertensive treatment be continued or stopped temporarily? Given the many types of stroke, and the wide range of blood pressures in patients with acute stroke, it may be wise to start by investigating the effects of blood-pressure lowering in hypertensive patients with primary intracerebral haemorrhage, in whom the association between blood pressure and the risk of stroke is strong. A positive result would provide a strong rationale for further studies on bloodpressure lowering in patients with hypertension and acute ischaemic stroke and in normotensive patients with primary intracerebral haemorrhage. Additional issues include the time window for initiation of treatment, target blood pressure, and the route of drug administration, particularly in patients with severe stroke and impaired consciousness. In the meantime, the ACCESS study should reassure investigators who are keen to examine these issues that careful studies are safe for the participants and that the potential gains in terms of lives saved and disability averted are substantial.5 John Chalmers Institute for International Health, University of Sydney (C37), 144-46 Burren Street, Sydney, NSW 2042, Australia. Email [email protected] Conflict of interest
JC was co-principal investigator for the Perindopril Protection Against Recurrent Stroke Study and an author of the International Society of Hypertension Statements on the management of blood pressure in acute stroke and on blood pressure lowering and stroke prevention. References 1 2 3
4
5
Bath P, Chalmers J, Powers W, et al. Statement on the management of blood pressure in acute stroke. J Hypertens 2003; 21: 665–72. Chalmers J, Todd A, Chapman N, et al. Statement on blood pressure lowering and stroke prevention. J Hypertens 2003; 21: 651–63. Chobanian AV, Bakris GL, Black HL, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003; 289: 2560–71. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure lowering regimen among 6105 patients with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41. Schrader J, Lüders S, Kulschewski A, et. al. The ACCESS Study: Evaluation of acute condensation cilexetil therapy in stroke survivors. Stroke 2003; 34: 1699–1703.
For personal use. Only reproduce with permission from The Lancet.
593