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
Por:
Best, JG, Ambler, G, Wilson, D, Lee, KJ, Lim, JS, Shiozawa, M, Koga, M, Li, LX, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, TJ, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Molad, J, Nishihara, M, Tanaka, J, Coutts, SB, Polymeris, A, Wagner, B, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, LJ, Salman, RAS, Jager, HR, Lip, GYH, Fischer, U, El-Koussy, M, Mas, JL, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Mess, WH, Nederkoorn, PJ, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, AC, Yatawara, C, Mendyk, AM, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, FE, Simister, R, Hendrikse, J, Kelly, PJ, Wardlaw, J, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Hara, H, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, HJ, Marti-Fabregas, J, Werring, DJ, Microbleeds Int Collaborative
Publicada:
1 abr 2021
Resumen:
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.
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. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Filiaciones:
Best, JG:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
Ambler, G:
UCL, Dept Stat Sci, Gower St, London, England
Wilson, D:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
New Zealand Brain Res Inst, Christchurch, New Zealand
Lee, KJ:
Seoul Natl Univ, Coll Med, Dept Neurol, Bundang Hosp, Seongnam, South Korea
Lim, JS:
Hallym Univ, Coll Med, Hallym Neurol Inst, Dept Neurol,Sacred Heart Hosp, Anyang, South Korea
Shiozawa, M:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Koga, M:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Li, LX:
Univ Oxford, Wolfson Ctr Prevent Stroke & Dementia, Nuffield Dept Clin Neurosci, Oxford, England
Lovelock, C:
Univ Oxford, Wolfson Ctr Prevent Stroke & Dementia, Nuffield Dept Clin Neurosci, Oxford, England
Chabriat, H:
Lariboisiere Hosp, Assistance Publ Hop Paris, Dept Neurol, Paris, France
Univ Paris, Federat Hosp Univ NeuroVasc, Paris, France
INSERM U1141, Paris, France
Hennerici, M:
Heidelberg Univ, Dept Neurol, Univ Med Mannheim, Mannheim, Germany
Wong, YK:
Univ Hong Kong, Dept Med, Div Neurol, Hong Kong, Peoples R China
Mak, HKF:
Univ Hong Kong, Dept Diagnost Radiol, Hong Kong, Peoples R China
Prats-Sanchez, L:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Martinez-Domeno, A:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Inamura, S:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Hokkaido, Japan
Yoshifuji, K:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Hokkaido, Japan
Arsava, EM:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging,Dept Neurol, Boston, MA 02115 USA
Horstmann, S:
Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany
Purrucker, J:
Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany
Lam, BYK:
Chinese Univ Hong Kong, Therese Pei Fong Chow Res Ctr Prevent Dementia, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Dept Med & Therapeut, Hong Kong, Peoples R China
Wong, A:
Chinese Univ Hong Kong, Therese Pei Fong Chow Res Ctr Prevent Dementia, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Dept Med & Therapeut, Hong Kong, Peoples R China
Kim, YD:
Yonsei Univ, Dept Neurol, Coll Med, Seoul, South Korea
Song, TJ:
Ewha Womans Univ, Seoul Hosp, Dept Neurol, Coll Med, Seoul, South Korea
Lemmens, R:
Katholieke Univ Leuven, Dept Neurosci, Expt Neurol, Leuven, Belgium
Univ Hosp Leuven, Ctr Brain & Dis Res Dept Neurol, Vlaams Inst Biotechnol, Leuven, Belgium
Univ Hosp Leuven, Dept Neurol, Leuven, Belgium
Eppinger, S:
Med Univ Graz, Dept Neurol, Graz, Austria
Gattringer, T:
Med Univ Graz, Dept Neurol, Graz, Austria
Uysal, E:
Saglik Bilimleri Univ, Sisli Etfal Educ & Res Hosp, Dept Radiol, Istanbul, Turkey
Tanriverdi, Z:
Izmir Katip Elebi Univ, Dept Neurol, Ataturk Educ & Res Hosp, Izmir, Turkey
Bornstein, NM:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Ben Assayag, E:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Hallevi, H:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Molad, J:
Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Nishihara, M:
Saga Univ, Dept Radiol, Fac Med, Saga, Japan
Tanaka, J:
Saga Univ, Dept Internal Med, Div Neurol, Fac Med, Saga, Japan
Coutts, SB:
Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci Radiol & Community Hlth Sci, Calgary, AB, Canada
Polymeris, A:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Wagner, B:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Seiffge, DJ:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Bern, Univ Hosp Inselspital Bern, Dept Neurol, Bern, Switzerland
Lyrer, P:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Algra, A:
Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
Univ Utrecht, Dept Neurol & Neurosurg, Utrecht, Netherlands
Kappelle, LJ:
Univ Utrecht, Dept Neurol & Neurosurg, Utrecht, Netherlands
Salman, RAS:
Univ Edinburgh, Ctr Clin Brain Sci, Sch Clin Sci, Edinburgh, Midlothian, Scotland
Jager, HR:
UCL, Lysholm Dept Neuroradiol, London, England
UCL, Neuroradiol Acad Unit, Dept Brain Repair & Rehabil, London, England
Inst Neurol, London, England
Natl Hosp Neurol & Neurosurg, London, England
Lip, GYH:
Univ Liverpool, Liverpool Ctr Cardiovasc Sci, Liverpool, Merseyside, England
Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England
Aalborg Univ, Dept Clin Med, Aalborg Thrombosis Res Unit, Aalborg, Denmark
Fischer, U:
Univ Bern, Univ Hosp Inselspital Bern, Dept Neurol, Bern, Switzerland
El-Koussy, M:
Univ Bern, Univ Hosp Inselspital Bern, Dept Diagnost & Intervent Neuroradiol, Bern, Switzerland
Mas, JL:
Univ Paris, Dept Neurol, INSERM, Inst Psychiat & Neurosci Paris,St Anne Hosp, Paris, France
Legrand, L:
Univ Paris, Dept Neuroradiol, Inst Psychiat & Neurosci Paris, St Anne Hosp,INSERM, Paris, France
Karayiannis, C:
Monash Univ, Peninsula Clin Sch, Peninsula Hlth, Melbourne, Vic, Australia
Phan, T:
Monash Univ, Sch Clin Sci, Stroke & Ageing Res Grp, Monash Hlth, Melbourne, Vic, Australia
Gunkel, S:
Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany
Christ, N:
Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany
Abrigo, J:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Imaging & Intervent Radiol, Hong Kong, Peoples R China
Leung, T:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Peoples R China
Chu, W:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Imaging & Intervent Radiol, Hong Kong, Peoples R China
Chappell, F:
Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh Imaging, Edinburgh, Midlothian, Scotland
Univ Edinburgh, UK Dementia Res Inst, Edinburgh, Midlothian, Scotland
Makin, S:
Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland
Hayden, D:
Univ Coll Dublin, Neurovasc Res Unit, Stroke Clin Trials Network Ireland, Dublin, Ireland
Univ Coll Dublin, Stroke Clin Trials Network Ireland, Hlth Res Board, Dublin, Ireland
Trinity Coll Dublin, Dept Med Gerontol, Dublin, Ireland
Williams, DJ:
Univ Med & Hlth Sci Dublin, Royal Coll Surg Ireland, Dept Geriatr & Stroke Med, Dublin, Ireland
Beaumont Hosp Dublin, Dept Geriatr & Stroke Med, Dublin, Ireland
Mess, WH:
Maastricht Univ Med Ctr, Dept Clin Neurophysiol, Maastricht, Netherlands
Nederkoorn, PJ:
Amsterdam Univ Med Ctr, Dept Neurol, Amsterdam, Netherlands
Barbato, C:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
Browning, S:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
Wiegertjes, K:
Radboud Univ Nijmegen Med Ctr, Donders Ctr Med Neurosci, Donders Inst Brain, Dept Neurol, Nijmegen, Netherlands
Tuladhar, AM:
Radboud Univ Nijmegen Med Ctr, Donders Ctr Med Neurosci, Donders Inst Brain, Dept Neurol, Nijmegen, Netherlands
Maaijwee, N:
Lucerne State Hosp, Neuroctr, Dept Neurol & Neurorehabil, Luzern, Switzerland
Guevarra, AC:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
Yatawara, C:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
Mendyk, AM:
Univ Lille, Ctr Hosp Univ Lille, INSERM, Degenerat & Vasc Cognit Disorders, Lille, France
Delmaire, C:
Univ Lille, Ctr Hosp Univ Lille, INSERM, Degenerat & Vasc Cognit Disorders, Lille, France
Fdn Adolphe De Rothschild, Dept Radiol, Paris, France
Kohler, S:
Maastricht Univ Med Ctr, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
van Oostenbrugge, R:
Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Dept Neurol, Maastricht, Netherlands
Zhou, Y:
Zhejiang Univ, Sch Med, Dept Neurol, Affiliated Hosp 2, Hangzhou, Peoples R China
Xu, C:
Zhejiang Univ, Sch Med, Dept Neurol, Affiliated Hosp 2, Hangzhou, Peoples R China
Hilal, S:
Natl Univ Singapore, Memory Aging & Cognit Ctr, Yong Loo Lin Sch Med, Singapore, Singapore
Gyanwali, B:
Natl Univ Singapore, Memory Aging & Cognit Ctr, Yong Loo Lin Sch Med, Singapore, Singapore
Chen, C:
Natl Univ Singapore, Memory Aging & Cognit Ctr, Yong Loo Lin Sch Med, Singapore, Singapore
Lou, M:
Zhejiang Univ, Sch Med, Dept Neurol, Affiliated Hosp 2, Hangzhou, Peoples R China
Staals, J:
Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Dept Neurol, Maastricht, Netherlands
Bordet, R:
Univ Lille, Ctr Hosp Univ Lille, INSERM, Degenerat & Vasc Cognit Disorders, Lille, France
Kandiah, N:
Natl Neurosci Inst, Dept Neurol, Singapore, Singapore
de Leeuw, FE:
Radboud Univ Nijmegen Med Ctr, Donders Ctr Med Neurosci, Donders Inst Brain, Dept Neurol, Nijmegen, Netherlands
Simister, R:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
Univ Coll London Hosp NHS Trust, Comprehens Stroke Serv, London, England
Hendrikse, J:
Univ Utrecht, Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands
Kelly, PJ:
Univ Coll Dublin, Neurovasc Res Unit, Stroke Clin Trials Network Ireland, Dublin, Ireland
Univ Coll Dublin, Stroke Clin Trials Network Ireland, Hlth Res Board, Dublin, Ireland
Wardlaw, J:
Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh Imaging, Edinburgh, Midlothian, Scotland
Univ Edinburgh, UK Dementia Res Inst, Edinburgh, Midlothian, Scotland
Soo, Y:
Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Peoples R China
Fluri, F:
Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany
Srikanth, V:
Monash Univ, Peninsula Clin Sch, Peninsula Hlth, Melbourne, Vic, Australia
Calvet, D:
Univ Paris, Dept Neurol, INSERM, Inst Psychiat & Neurosci Paris,St Anne Hosp, Paris, France
Jung, S:
Univ Bern, Univ Hosp Inselspital Bern, Dept Neurol, Bern, Switzerland
Kwa, VIH:
Onze Lieve Vrouw Hosp, Dept Neurol, Amsterdam, Netherlands
Engelter, ST:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Basel, Dept Geriatr Med FELIX PLATTER, Neurol & Neurorehabil, Basel, Switzerland
Peters, N:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Univ Hosp Basel, Stroke Ctr, Basel, Switzerland
Univ Basel, Basel, Switzerland
Univ Basel, Dept Geriatr Med FELIX PLATTER, Neurol & Neurorehabil, Basel, Switzerland
Smith, EE:
Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci Radiol & Community Hlth Sci, Calgary, AB, Canada
Hara, H:
Saga Univ, Dept Internal Med, Div Neurol, Fac Med, Saga, Japan
Yakushiji, Y:
Saga Univ, Dept Internal Med, Div Neurol, Fac Med, Saga, Japan
Kansai Med Univ, Dept Neurol, Osaka, Japan
Orken, DN:
Mem Sisli Hosp, Dept Neurol, Istanbul, Turkey
Fazekas, F:
Med Univ Graz, Dept Neurol, Graz, Austria
Thijs, V:
Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Heidelberg, Vic, Australia
Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia
Heo, JH:
Yonsei Univ, Dept Neurol, Coll Med, Seoul, South Korea
Mok, V:
Chinese Univ Hong Kong, Therese Pei Fong Chow Res Ctr Prevent Dementia, Gerald Choa Neurosci Ctr, Lui Che Woo Inst Innovat Med,Dept Med & Therapeut, Hong Kong, Peoples R China
Veltkamp, R:
Heidelberg Univ Hosp, Dept Neurol, Heidelberg, Germany
Imperial Coll London, Dept Brain Sci, London, England
Ay, H:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging,Dept Neurol, Boston, MA 02115 USA
Takeda, Cambridge, MA USA
Imaizumi, T:
Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Hokkaido, Japan
Gomez-Anson, B:
Hosp Santa Creu & Sant Pau, Unit Neuroradiol, Biomed Res Inst, Barcelona, Spain
Lau, KK:
Univ Hong Kong, Dept Med, Div Neurol, Hong Kong, Peoples R China
Jouvent, E:
Lariboisiere Hosp, Assistance Publ Hop Paris, Dept Neurol, Paris, France
Univ Paris, Federat Hosp Univ NeuroVasc, Paris, France
INSERM U1141, Paris, France
Rothwell, PM:
Univ Oxford, Wolfson Ctr Prevent Stroke & Dementia, Nuffield Dept Clin Neurosci, Oxford, England
Toyoda, K:
Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
Bae, HJ:
Seoul Natl Univ, Coll Med, Dept Neurol, Bundang Hosp, Seongnam, South Korea
Marti-Fabregas, J:
Hosp Santa Creu & Sant Pau, Dept Neurol, Biomed Res Inst, Barcelona, Spain
Werring, DJ:
UCL, Dept Brain Repair & Rehabil, UCL Stroke Res Ctr, Queen Sq Inst Neurol, London WC1B SEH, England
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