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Effects of Candesartan in the Acute Phase of Intracerebral Hemorrhage
Authors:Mirza Jusufovic  Trude Elisabeth Berge  Rui Guo  Shoujiang You  Candice Delcourt  Craig Anderson  Philip M. Bath  Björn W. Karlson  Eivind Berge  Else Charlotte Sandset
Affiliation:2. Faculty of Medicine, University of Oslo, Oslo, Norway;3. Faculty of Medicine, George Institute for Global Health, UNSW, Sydney, New South Wales, Australia;4. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China;5. Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia;11. Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK;12. AstraZeneca R&D, Mölndal, Sweden;8. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;9. Stroke Unit, Oslo University Hospital, Oslo, Norway
Abstract:Background and Purpose: Uncertainty persists over the effects of blood pressure-lowering treatment in acute intracerebral hemorrhage (ICH). We assessed the effects of treatment with candesartan in acute ICH and according to different types of hematoma. Methods: Post-hoc analysis of the Scandinavian Candesartan Acute Stroke Trial, a randomized- and placebo-controlled, double-masked trial of candesartan in patients with any stroke within the acute phase (<30 hours) and high systolic blood pressure (≥140 mm Hg). We collected baseline computed tomography scans of participants with ICH, and characterized hematoma volume (planimetric approach), location (deep versus lobar or infratentorial), hemisphere side, and presence of intraventricular hemorrhage. The trial's 2 coprimary effect variables were the composite endpoint of vascular death, stroke or myocardial infarction, and functional outcome at 6 months according to the modified Rankin scale. We used Cox, ordinal, and binary logistic regression for analysis and adjusted for key, predefined prognostic variables. Results: Of 274 participants with ICH, computed tomography scans were available in 205 patients (74.8%). There were no significant differences between the candesartan and placebo groups with respect to hematoma volume (median 15.6 mL versus 13.5 mL, P = .96), deep location (77% versus 72%, P = .64), right hemisphere (49% versus 51%, P = .46), and presence of intraventricular hemorrhage (18% versus 11%, P = .22). Candesartan was associated with a significant increase in poor functional outcome in patients with deep hematoma (adjusted common odds ratio 2.27, 95% confidence interval 1.23-4.18, P = .009, P for interaction .015), but there was no differential effect on functional outcome or vascular events in any of the other imaging subgroups. Conclusions: Candesartan was not associated with any beneficial effect when initiated in the acute phase of ICH, a possible adverse effect on functional outcome in patients with deep hematomas cannot be ruled out by this study alone.
Keywords:Scandinavian Candesartan Acute Stroke Trial (SCAST) Study Group  Acute stroke  intracerebral hemorrhage  blood pressure  candesartan
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