TY - JOUR
T1 - Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack
T2 - a pooled analysis of individual patient data from cohort studies
AU - Microbleeds International Collaborative Network
AU - Best, Jonathan G.
AU - Ambler, Gareth
AU - Wilson, Duncan
AU - Lee, Keon Joo
AU - Lim, Jae Sung
AU - Shiozawa, Masayuki
AU - Koga, Masatoshi
AU - Li, Linxin
AU - Lovelock, Caroline
AU - Chabriat, Hugues
AU - Hennerici, Michael
AU - Wong, Yuen Kwun
AU - Mak, Henry Ka Fung
AU - Prats-Sanchez, Luis
AU - Martínez-Domeño, Alejandro
AU - Inamura, Shigeru
AU - Yoshifuji, Kazuhisa
AU - Arsava, Ethem Murat
AU - Horstmann, Solveig
AU - Purrucker, Jan
AU - Lam, Bonnie Yin Ka
AU - Wong, Adrian
AU - Kim, Young Dae
AU - Song, Tae Jin
AU - Lemmens, Robin
AU - Eppinger, Sebastian
AU - Gattringer, Thomas
AU - Uysal, Ender
AU - Tanriverdi, Zeynep
AU - Bornstein, Natan M.
AU - Ben Assayag, Einor
AU - Hallevi, Hen
AU - Molad, Jeremy
AU - Nishihara, Masashi
AU - Tanaka, Jun
AU - Coutts, Shelagh B.
AU - Polymeris, Alexandros
AU - Wagner, Benjamin
AU - Seiffge, David J.
AU - Lyrer, Philippe
AU - Algra, Ale
AU - Kappelle, L. Jaap
AU - Al-Shahi Salman, Rustam
AU - Jäger, Hans R.
AU - Lip, Gregory Y.H.
AU - Fischer, Urs
AU - El-Koussy, Marwan
AU - Mas, Jean Louis
AU - Legrand, Laurence
AU - Karayiannis, Christopher
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4
Y1 - 2021/4
N2 - Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69–0·77) with a calibration slope of 0·94 (0·81–1·06) for the intracranial haemorrhage model and 0·63 (0·62–0·65) with a calibration slope of 0·97 (0·87–1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. Funding: British Heart Foundation and Stroke Association.
AB - Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69–0·77) with a calibration slope of 0·94 (0·81–1·06) for the intracranial haemorrhage model and 0·63 (0·62–0·65) with a calibration slope of 0·97 (0·87–1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. Funding: British Heart Foundation and Stroke Association.
UR - http://www.scopus.com/inward/record.url?scp=85102586910&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(21)00024-7
DO - 10.1016/S1474-4422(21)00024-7
M3 - Article
C2 - 33743239
AN - SCOPUS:85102586910
SN - 1474-4422
VL - 20
SP - 294
EP - 303
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 4
ER -