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 - 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

AU - Emsley, Hedley

PY - 2021/4/30

Y1 - 2021/4/30

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.  

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.  

U2 - 10.1016/S1474-4422(21)00024-7

DO - 10.1016/S1474-4422(21)00024-7

M3 - Journal article

C2 - 33743239

AN - SCOPUS:85102586910

VL - 20

SP - 294

EP - 303

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 4

ER -