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

Best, Jonathan G. and Ambler, Gareth and Wilson, Duncan and Lee, Keon-Joo and Lim, Jae-Sung and Shiozawa, Masayuki and Koga, Masatoshi and Li, Linxin and Lovelock, Caroline and Chabriat, Hugues and Hennerici, Michael and Wong, Yuen Kwun and Mak, Henry Ka Fung and Prats-Sanchez, Luis and Martínez-Domeño, Alejandro and Inamura, Shigeru and Yoshifuji, Kazuhisa and Arsava, Ethem Murat and Horstmann, Solveig and Purrucker, Jan and Lam, Bonnie Yin Ka and Wong, Adrian and Kim, Young Dae and Song, Tae-Jin and Lemmens, Robin and Eppinger, Sebastian and Gattringer, Thomas and Uysal, Ender and Tanriverdi, Zeynep and Bornstein, Natan M. and Ben Assayag, Einor and Hallevi, Hen and Molad, Jeremy and Nishihara, Masashi and Tanaka, Jun and Coutts, Shelagh B. and Polymeris, Alexandros and Wagner, Benjamin and Seiffge, David J. and Lyrer, Philippe and Algra, Ale and Kappelle, L. Jaap and Al-Shahi Salman, Rustam and Jäger, Hans R. and Lip, Gregory Y. H. and Fischer, Urs and El-Koussy, Marwan and Mas, Jean-Louis and Legrand, Laurence and Karayiannis, Christopher and Phan, Thanh and Gunkel, Sarah and Christ, Nicolas and Abrigo, Jill and Leung, Thomas and Chu, Winnie and Chappell, Francesca and Makin, Stephen and Hayden, Derek and Williams, David J. and Mess, Werner H. and Nederkoorn, Paul J. and Barbato, Carmen and Browning, Simone and Wiegertjes, Kim and Tuladhar, Anil M. and Maaijwee, Noortje and Guevarra, Anne Cristine and Yatawara, Chathuri and Mendyk, Anne-Marie and Delmaire, Christine and Köhler, Sebastian and van Oostenbrugge, Robert and Zhou, Ying and Xu, Chao and Hilal, Saima and Gyanwali, Bibek and Chen, Christopher and Lou, Min and Staals, Julie and Bordet, Régis and Kandiah, Nagaendran and de Leeuw, Frank-Erik and Simister, Robert and Hendrikse, Jeroen and Kelly, Peter J. and Wardlaw, Joanna and Soo, Yannie and Fluri, Felix and Srikanth, Velandai and Calvet, David and Jung, Simon and Kwa, Vincent I. H. and Engelter, Stefan T. and Peters, Nils and Smith, Eric E. and Hara, Hideo and Yakushiji, Yusuke and Orken, Dilek Necioglu and Fazekas, Franz and Thijs, Vincent and Heo, Ji Hoe and Mok, Vincent and Veltkamp, Roland and Ay, Hakan and Imaizumi, Toshio and Gomez-Anson, Beatriz and Lau, Kui Kai and Jouvent, Eric and Rothwell, Peter M. and Toyoda, Kazunori and Bae, Hee-Joon and Marti-Fabregas, Joan and Werring, David J.. (2021) 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. The Lancet. Neurology, 20 (4). pp. 294-303.

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Official URL: https://edoc.unibas.ch/84727/

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Abstract

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.

Faculties and Departments:	03 Faculty of Medicine
UniBasel Contributors:	Polymeris, Alexandros
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Elsevier
ISSN:	1474-4465
Note:	Publication type according to Uni Basel Research Database: Journal article
Identification Number:	doi: 10.1016/S1474-4422(21)00024-7 pmid: 33743239
Last Modified:	06 May 2022 15:19
Deposited On:	06 May 2022 15:19

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