The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial

• Published in: The Lancet (British edition) Vol. 377; no. 9767; pp. 741 - 750
• Main Authors: Sandset, Else Charlotte, MD, Bath, Philip MW, Prof, Boysen, Gudrun, Prof, Jatuzis, Dalius, MD, Kõrv, Janika, MD, Lüders, Stephan, MD, Murray, Gordon D, Prof, Richter, Przemyslaw S, MD, Roine, Risto O, Prof, Terént, Andreas, Prof, Thijs, Vincent, MD, Berge, Eivind, Dr
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 2011; Elsevier; Elsevier Limited
• Subjects: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin II Type 1 Receptor Blockers - adverse effects; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Biological and medical sciences; Biphenyl Compounds; Blood pressure; Blood Pressure - drug effects; Brain Ischemia - complications; Cerebral Hemorrhage - complications; Clinical medicine; composite materials; death; Double-Blind Method; Drug Administration Schedule; Drug therapy; Europe; Female; General aspects; Hospitals; Humans; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; hypotension; Internal Medicine; Male; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Meta-Analysis as Topic; Middle Aged; Mortality; Myocardial infarction; Neurology; Odds Ratio; patients; Regression Analysis; renal failure; risk; Stroke; Stroke - drug therapy; Stroke - etiology; Stroke - physiopathology; Studies; systolic blood pressure; Tetrazoles - administration & dosage; Tetrazoles - adverse effects; Treatment Failure; Vascular diseases and vascular malformations of the nervous system; Norway; Europe; Norway, Oslo; Imidazole derivatives; Tetrazole derivatives; Nervous system diseases; Stroke; Candesartan; Acute; Peptide hormone; Cardiovascular disease; Randomized controlled trial; Cerebral disorder; Vascular disease; Medicine; Octapeptide; Renin angiotensin system; Treatment; Biphenyl derivatives; Central nervous system disease; Double blind study; Antihypertensive agent; Clinical trial; Sartan derivatives; Angiotensin antagonist; Angiotensin II; Cerebrovascular disease
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(11)60104-9

Summary 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.