TY - JOUR
T1 - The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST)
T2 - a randomised, placebo-controlled, double-blind trial
AU - Sandset, Else Charlotte
AU - Bath, Philip M W
AU - Boysen, Gudrun
AU - Jatuzis, Dalius
AU - Kõrv, Janika
AU - Lüders, Stephan
AU - Murray, Gordon D
AU - Richter, Przemyslaw S
AU - Roine, Risto O
AU - Terént, Andreas
AU - Thijs, Vincent
AU - Berge, Eivind
AU - SCAST Study Group
AU - Iversen, Helle Klingenberg
N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.
PY - 2011/2/26
Y1 - 2011/2/26
N2 - BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure.METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 (ClinicalTrials.gov), and ISRCTN13643354.FINDINGS: 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [SD 23/14] in the candesartan group on day 7 vs 152/84 mm Hg [22/14] in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84-1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00-1·38; p=0·048 [not significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo.INTERPRETATION: There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect.FUNDING: South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.
AB - BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure.METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 (ClinicalTrials.gov), and ISRCTN13643354.FINDINGS: 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [SD 23/14] in the candesartan group on day 7 vs 152/84 mm Hg [22/14] in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84-1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00-1·38; p=0·048 [not significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo.INTERPRETATION: There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect.FUNDING: South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.
KW - Aged
KW - Aged, 80 and over
KW - Angiotensin II Type 1 Receptor Blockers
KW - Antihypertensive Agents
KW - Benzimidazoles
KW - Blood Pressure
KW - Brain Ischemia
KW - Cerebral Hemorrhage
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Europe
KW - Female
KW - Humans
KW - Hypertension
KW - Male
KW - Meta-Analysis as Topic
KW - Middle Aged
KW - Odds Ratio
KW - Regression Analysis
KW - Stroke
KW - Tetrazoles
KW - Treatment Failure
U2 - 10.1016/S0140-6736(11)60104-9
DO - 10.1016/S0140-6736(11)60104-9
M3 - Journal article
C2 - 21316752
VL - 377
SP - 741
EP - 750
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9767
ER -