TY - JOUR
T1 - Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy
T2 - international individual patient data pooled analysis
AU - Hostettler, Isabel Charlotte
AU - Wilson, Duncan
AU - Fiebelkorn, Catherine Arnold
AU - Aum, Diane
AU - Ameriso, Sebastián Francisco
AU - Eberbach, Federico
AU - Beitzke, Markus
AU - Kleinig, Timothy
AU - Phan, Thanh
AU - Marchina, Sarah
AU - Schneckenburger, Romain
AU - Carmona-Iragui, Maria
AU - Charidimou, Andreas
AU - Mourand, Isabelle
AU - Parreira, Sara
AU - Ambler, Gareth
AU - Jäger, Hans Rolf
AU - Singhal, Shaloo
AU - Ly, John
AU - Ma, Henry
AU - Touzé, Emmanuel
AU - Geraldes, Ruth
AU - Fonseca, Ana Catarina
AU - Melo, Teresa
AU - Labauge, Pierre
AU - Lefèvre, Pierre Henry
AU - Viswanathan, Anand
AU - Greenberg, Steven Mark
AU - Fortea, Juan
AU - Apoil, Marion
AU - Boulanger, Marion
AU - Viader, Fausto
AU - Kumar, Sandeep
AU - Srikanth, Velandai
AU - Khurram, Ashan
AU - Fazekas, Franz
AU - Bruno, Veronica
AU - Zipfel, Gregory Joseph
AU - Refai, Daniel
AU - Rabinstein, Alejandro
AU - Graff-Radford, Jonathan
AU - Werring, David John
N1 - Funding Information:
ICH received funding from the Alzheimer Research UK and Dunhill Medical Trust Foundation. DW received funding from the Stroke Foundation/British Heart Foundation. CAF reports no disclosures. DA reports no disclosures. SFA reports no disclosures. FE reports no disclosures. MB reports no disclosures. TK reports no disclosures. TP has received Honorarium as speaker from Genzyme, Boehringer Ingelheim, Pfizer, BMS, Bayer. Dr. P is also on the Advisory Board for Genzyme on Fabry disease. SM reports no disclosures. RS reports no disclosures. MCI reports grants from Instituto de Salud Carlos III, grants from the Alzheimer’s Association and the Global Brain Health Institute, grants from Jérome Lejeune Foundation, grants from Societat Catalana de Neurologia, and non-financial support from Fundació Catalana Síndrome de Down during the conduct of the study. AC reports no disclosures. IM reports no disclosures. SP reports no disclosures. GA reports no disclosures. HRJ reports no disclosures. SS reports no disclosures. JL reports no disclosures. HM reports no disclosures. ET reports no disclosures. RG reports no disclosures. ACF reports no disclosures. TM reports no disclosures. PL reports no disclosures. PHL reports no disclosures. AV reports no disclosures. SMG is a consultant for Hoffmann-LaRoche and GlaxoSmithKline. Dr. G is on the data monitoring committee of Biogen and the Data Safety Monitoring Board at Washington University/IQVIA. He is on the Editorial Board of following journals: Stroke, Cerebrovascular Disease, Neurology and American Journal of Alzheimer’s Disease and Other dementias. He is additionally a Section Editor for Stroke. Dr. Greenberg receives royalties from UpToDate and is funded by following NIH grants: #R01NS096730, #R01AG026484, #U24 NS107154, #U24 NS100591. JF reports grants from Instituto de Salud Carlos III, grants from Fundació Marató TV3, grants from NIH, grants from Departament de Salut de la Generalitat de Catalunya, grants from Jérome Lejeune Foundation, grants from Fundació Víctor Grífols i Lucas, and non-financial support from Fundació Catalana Síndrome de Down during the conduct of the study; personal fees from AC Inmune Clinical Advisory Board, personal fees from Novartis Adjudication Committee, personal fees from Lundbeck Advisory Board, personal fees from Esteve Conference fees, personal fees from NovoNordisk Conference fees, personal fees from Roche Conference fees and advisory board, personal fees from Fujirebio Conference fees, personal fees from Biogen Conference fees, and personal fees from Merck Adjudication Committee outside the submitted work; in addition, Dr. Fortea has a patent for Markers of synaptopathy in neurodegenerative disease licensed EP18382175.0. MA reports no disclosures. MB reports no disclosures. FV reports no disclosures. SK reports no disclosures. VS reports no disclosures. AK reports no disclosures. FF reports no disclosures. VB reports no disclosures. GJZ reports no disclosures. DR reports no disclosures. AR is a member of the external committee for adverse event adjudication for PREVAIL trial/CAP2 registry. Dr. R is on the editorial board Neurology, Neurocritical Care, Stroke and CONTINUUM. He receives royalties for: Practical Neuroimaging in Stroke—Elsevier—2009 What To Do? Neurocritical Care—Oxford—2016. JG-R is funded by an NIH grant: #K76 AG057015-01. DJW received funding from the Stroke Foundation/British Heart Foundation. Dr. W reports personal fees from Bayer, Alnylam and Portola.
Funding Information:
This study was not funded and did not receive industry sponsoring. ICH received funding from the Alzheimer Research UK and Dunhill Medical Trust Foundation. DJW and DW receive funding from the Stroke Foundation/British Heart Foundation. This work was undertaken at UCLH/UCL which receives a proportion of funding from the Department of Health’s National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - Objective: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). Methods: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. Results: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9–17.4); recurrent cSAH 11.1% (95% CI 7.9–15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7–26.9), ischemic stroke 5.1% (95% CI 3.1–8) and death 8.3% (95% CI 5.6–11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13–75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84–15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17–1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16–1.78, p = 0.31). Conclusions: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.
AB - Objective: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). Methods: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. Results: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9–17.4); recurrent cSAH 11.1% (95% CI 7.9–15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7–26.9), ischemic stroke 5.1% (95% CI 3.1–8) and death 8.3% (95% CI 5.6–11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13–75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84–15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17–1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16–1.78, p = 0.31). Conclusions: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.
KW - Cerebral amyloid angiopathy
KW - Intracerebral haemorrhage
KW - Ischemic stroke
KW - Non-traumatic convexity/convexal/cortical subarachnoid haemorrhage
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85111091526&partnerID=8YFLogxK
U2 - 10.1007/s00415-021-10706-3
DO - 10.1007/s00415-021-10706-3
M3 - Article
C2 - 34272978
AN - SCOPUS:85111091526
SN - 0340-5354
VL - 269
SP - 1427
EP - 1438
JO - Journal of Neurology
JF - Journal of Neurology
IS - 3
ER -