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: a pooled analysis of individual patient data from cohort studies.

2021-04-20

Best, Jonathan G

Ambler, Gareth

Wilson, Duncan

Lee, Keon-Joo

Lim, Jae-Sung

Shiozawa, Masayuki

Koga, Masatoshi

Li, Linxin

Lovelock, Caroline

Chabriat, Hugues

Hennerici, Michael

Wong, Yuen Kwun

Mak, Henry Ka Fung

Prats-Sanchez, Luis

Martínez-Domeño, Alejandro

Inamura, Shigeru

Yoshifuji, Kazuhisa

Arsava, Ethem Murat

Horstmann, Solveig

Purrucker, Jan

Lam, Bonnie Yin Ka

Wong, Adrian

Kim, Young Dae

Song, Tae-Jin

Lemmens, Robin

Eppinger, Sebastian

Gattringer, Thomas

Uysal, Ender

Tanriverdi, Zeynep

Bornstein, Natan M

Ben Assayag, Einor

Hallevi, Hen

Molad, Jeremy

Nishihara, Masashi

Tanaka, Jun

Coutts, Shelagh B

Polymeris, Alexandros

Wagner, Benjamin

Seiffge, David J

Lyrer, Philippe

Algra, Ale

Kappelle, L Jaap

Al-Shahi Salman, Rustam

Jäger, Hans R

Lip, Gregory Y H

Fischer, Urs

El-Koussy, Marwan

Mas, Jean-Louis

Legrand, Laurence

Karayiannis, Christopher

Phan, Thanh

Gunkel, Sarah

Christ, Nicolas

Abrigo, Jill

Leung, Thomas

Chu, Winnie

Chappell, Francesca

Makin, Stephen

Hayden, Derek

Williams, David J

Mess, Werner H

Nederkoorn, Paul J

Barbato, Carmen

Browning, Simone

Wiegertjes, Kim

Tuladhar, Anil M

Maaijwee, Noortje

Guevarra, Anne Cristine

Yatawara, Chathuri

Mendyk, Anne-Marie

Delmaire, Christine

Köhler, Sebastian

van Oostenbrugge, Robert

Zhou, Ying

Xu, Chao

Hilal, Saima

Gyanwali, Bibek

Chen, Christopher

Lou, Min

Staals, Julie

Bordet, Régis

Kandiah, Nagaendran

de Leeuw, Frank-Erik

Simister, Robert

Hendrikse, Jeroen

Kelly, Peter J

Wardlaw, Joanna

Soo, Yannie

Fluri, Felix

Srikanth, Velandai

Calvet, David

Jung, Simon

Kwa, Vincent I H

Engelter, Stefan T

Peters, Nils

Smith, Eric E

Hara, Hideo

Yakushiji, Yusuke

Orken, Dilek Necioglu

Fazekas, Franz

Thijs, Vincent N

Heo, Ji Hoe

Mok, Vincent

Veltkamp, Roland

Ay, Hakan

Imaizumi, Toshio

Gomez-Anson, Beatriz

Lau, Kui Kai

Jouvent, Eric

Rothwell, Peter M

Toyoda, Kazunori

Bae, Hee-Joon

Marti-Fabregas, Joan

Werring, David J

Journal Article

10.1016/S1474-4422(21)00024-7

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. 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. 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. 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. British Heart Foundation and Stroke Association.

link

The Lancet. Neurology 2021; 20(4): 294-303

The Lancet. Neurology