Effects of Candesartan in the Acute Phase of Intracerebral Hemorrhage

Mirza Jusufovic; Trude Elisabeth Berge; Rui Guo; Shoujiang You; Candice Delcourt; Craig Anderson; Philip M Bath; Björn W Karlson; Eivind Berge; Else Charlotte Sandset; Scandinavian Candesartan Acute Stroke Trial (SCAST) Study Group

doi:10.1016/j.jstrokecerebrovasdis.2019.05.010

Effects of Candesartan in the Acute Phase of Intracerebral Hemorrhage

J Stroke Cerebrovasc Dis. 2019 Aug;28(8):2262-2267. doi: 10.1016/j.jstrokecerebrovasdis.2019.05.010. Epub 2019 Jun 6.

Affiliations

¹ Department of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: mirza.jusufovic@medisin.uio.no.
² Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Faculty of Medicine, George Institute for Global Health, UNSW, Sydney, New South Wales, Australia; Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁵ Faculty of Medicine, George Institute for Global Health, UNSW, Sydney, New South Wales, Australia; Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia.
⁶ Faculty of Medicine, George Institute for Global Health, UNSW, Sydney, New South Wales, Australia; Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia; The George Institute for Global Health at Peking University Health Science Center, Beijing, China.
⁷ Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.
⁸ AstraZeneca R&D, Mölndal, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹ Departments of Internal Medicine and Cardiology, Oslo University Hospital, Oslo, Norway.
¹⁰ Stroke Unit, Oslo University Hospital, Oslo, Norway; Research and Development Department, The Norwegian Air Ambulance Foundation, Oslo, Norway.

PMID: 31178359
DOI: 10.1016/j.jstrokecerebrovasdis.2019.05.010

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: Acute stroke; blood pressure; candesartan; intracerebral hemorrhage.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Angiotensin II Type 1 Receptor Blockers / adverse effects
Angiotensin II Type 1 Receptor Blockers / therapeutic use*
Antihypertensive Agents / adverse effects
Antihypertensive Agents / therapeutic use*
Benzimidazoles / adverse effects
Benzimidazoles / therapeutic use*
Biphenyl Compounds
Blood Pressure / drug effects*
Cerebral Hemorrhage / diagnostic imaging
Cerebral Hemorrhage / drug therapy*
Cerebral Hemorrhage / physiopathology
Double-Blind Method
Female
Hematoma / diagnostic imaging
Hematoma / drug therapy*
Hematoma / physiopathology
Humans
Male
Middle Aged
Scandinavian and Nordic Countries
Tetrazoles / adverse effects
Tetrazoles / therapeutic use*
Time Factors
Tomography, X-Ray Computed
Treatment Outcome

Substances

Angiotensin II Type 1 Receptor Blockers
Antihypertensive Agents
Benzimidazoles
Biphenyl Compounds
Tetrazoles
candesartan