Fast track — ArticlesThe angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial
Introduction
Raised blood pressure is common in patients with acute stroke, and is associated with poor short-term and long-term outcomes.1, 2, 3 The hypertensive response can have several causes, including inadequately treated or undiagnosed hypertension, stress response with activation of neuroendocrine systems, damage to autonomic centres in the brain, and increased intracranial pressure.4
The optimum management of blood pressure in acute stroke is not known,5 and current practice is to accept high blood pressure in this situation.6, 7, 8 Under normal circumstances, cerebral autoregulation sustains constant cerebral blood flow across an extensive range of systemic blood pressures.9 In acute stroke, the autoregulatory mechanism can be impaired or damaged, and cerebral tissue perfusion relies on systemic blood pressure. In this situation, blood-pressure reduction can compromise perfusion of the penumbra and cause further infarction, as suggested by a small trial of intravenous nimodipine.10 Conversely, high blood pressure can cause brain oedema or haemorrhage, and data from the International Stroke Trial2 showed a clear association between systolic blood pressure in the acute phase and early death and poor long-term outcome.
The angiotensin-receptor blocker candesartan has shown promising effects on infarct size and neurological status in several experimental studies.11, 12 The ACCESS study13 of 342 patients with acute stroke and high blood pressure suggested that treatment with candesartan during the first week of stroke reduces the incidence of vascular events and deaths during the first 12 months (odds ratio [OR] 0·48, 95% CI 0·25–0·90). The mechanisms by which angiotensin-receptor blockers can affect the risk of death and vascular events are unknown. Studies of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers in cardiovascular disease suggest specific neuroprotective effects beyond the effects of blood-pressure lowering,14, 15, 16 but whether similar effects can be seen in acute stroke remains to be shown. We aimed to assess whether careful blood-pressure lowering treatment with candesartan is beneficial in a wide range of patients with acute stroke and raised blood pressure.
Section snippets
Study design and participants
The Scandinavian Candesartan Acute Stroke Trial (SCAST) was a north European, multicentre, randomised, placebo-controlled, double-blind trial of candesartan in patients with acute stroke and raised blood pressure. Details of the design have been reported elsewhere.17 Patients aged 18 years or older with a clinical diagnosis of stroke (ischaemic or haemorrhagic), presenting within 30 h of symptom onset and with systolic blood pressure higher than 140 mm Hg were potential candidates for
Results
2029 patients were recruited from 146 centres in Belgium, Denmark, Estonia, Finland, Germany, Lithuania, Norway, Poland, and Sweden between June 5, 2005, and Feb 25, 2010 (figure 1). Patient recruitment was stopped before the intended sample size was reached because recruitment was slower than had been expected and the research grant expired. The decision to stop patient recruitment was made in May, 2009, by the trial steering committee. It was based purely on administrative grounds, without
Discussion
In this trial, we noted no beneficial effect of blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan in patients with acute stroke and raised blood pressure. For functional outcome, one of the two co-primary effect variables, the distribution of mRS scores at 6 months was less favourable for patients treated with candesartan than for those on placebo, but the difference was not significant because the p value (0·048) was greater than the threshold of 0·025
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