title: The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.
authors.affiliation: Department of Internal Medicine, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Else Charlotte
authors.initials: EC
authors.lastname: Sandset
authors.forename: Philip M W
authors.initials: PM
authors.lastname: Bath
authors.forename: Gudrun
authors.initials: G
authors.lastname: Boysen
authors.forename: Dalius
authors.initials: D
authors.lastname: Jatuzis
authors.forename: Janika
authors.initials: J
authors.lastname: Kõrv
authors.forename: Stephan
authors.initials: S
authors.lastname: Lüders
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Murray
authors.forename: Przemyslaw S
authors.initials: PS
authors.lastname: Richter
authors.forename: Risto O
authors.initials: RO
authors.lastname: Roine
authors.forename: Andreas
authors.initials: A
authors.lastname: Terént
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.forename: Eivind
authors.initials: E
authors.lastname: Berge
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D002545:Brain Ischemia / Q000150:complications; D002543:Cerebral Hemorrhage / Q000150:complications; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D017211:Treatment Failure
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan