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.
Journal
The Lancet. Neurology
ISSN: 1474-4465
Titre abrégé: Lancet Neurol
Pays: England
ID NLM: 101139309
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
29
05
2020
revised:
16
12
2020
accepted:
08
01
2021
pubmed:
21
3
2021
medline:
7
4
2021
entrez:
20
3
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 33743239
pii: S1474-4422(21)00024-7
doi: 10.1016/S1474-4422(21)00024-7
pii:
doi:
Substances chimiques
Fibrinolytic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
294-303Subventions
Organisme : Medical Research Council
ID : G1002605
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Investigateurs
Kirsty Harkness
(K)
Louise Shaw
(L)
Jane Sword
(J)
Azlisham Mohd Nor
(A)
Pankaj Sharma
(P)
Deborah Kelly
(D)
Frances Harrington
(F)
Marc Randall
(M)
Matthew Smith
(M)
Karim Mahawish
(K)
Abduelbaset Elmarim
(A)
Bernard Esisi
(B)
Claire Cullen
(C)
Arumug Nallasivam
(A)
Christopher Price
(C)
Adrian Barry
(A)
Christine Roffe
(C)
John Coyle
(J)
Ahamad Hassan
(A)
Jonathan Birns
(J)
David Cohen
(D)
Lakshmanan Sekaran
(L)
Adrian Parry-Jones
(A)
Anthea Parry
(A)
David Hargroves
(D)
Harald Proschel
(H)
Prabel Datta
(P)
Khaled Darawil
(K)
Aravindakshan Manoj
(A)
Mathew Burn
(M)
Chris Patterson
(C)
Elio Giallombardo
(E)
Nigel Smyth
(N)
Syed Mansoor
(S)
Ijaz Anwar
(I)
Rachel Marsh
(R)
Sissi Ispoglou
(S)
Dinesh Chadha
(D)
Mathuri Prabhakaran
(M)
Sanjeevikumar Meenakishundaram
(S)
Janice O'Connell
(J)
Jon Scott
(J)
Vinodh Krishnamurthy
(V)
Prasanna Aghoram
(P)
Michael McCormick
(M)
Nikola Sprigg
(N)
Paul O'Mahony
(P)
Martin Cooper
(M)
Lillian Choy
(L)
Peter Wilkinson
(P)
Simon Leach
(S)
Sarah Caine
(S)
Ilse Burger
(I)
Gunaratam Gunathilagan
(G)
Paul Guyler
(P)
Hedley Emsley
(H)
Michelle Davis
(M)
Dulka Manawadu
(D)
Kath Pasco
(K)
Maam Mamun
(M)
Robert Luder
(R)
Mahmud Sajid
(M)
Ijaz Anwar
(I)
James Okwera
(J)
Elizabeth Warburton
(E)
Kari Saastamoinen
(K)
Timothy England
(T)
Janet Putterill
(J)
Enrico Flossman
(E)
Michael Power
(M)
Krishna Dani
(K)
David Mangion
(D)
Appu Suman
(A)
John Corrigan
(J)
Enas Lawrence
(E)
Djamil Vahidassr
(D)
Clare Shakeshaft
(C)
Martin Brown
(M)
Andreas Charidimou
(A)
Hannah Cohen
(H)
Gargi Banerjee
(G)
Henry Houlden
(H)
Mark White
(M)
Tarek Yousry
(T)
Kirsty Harkness
(K)
Enrico Flossmann
(E)
Nigel Smyth
(N)
Louise Shaw
(L)
Elizabeth Warburton
(E)
Keith Muir
(K)
Pascal Gratz
(P)
Heinrich Mattle
(H)
Leonidas Panos
(L)
Amos Korczyn
(A)
Efrat Kliper
(E)
Philippe Maeder
(P)
Achim Gass
(A)
Chahin Pachai
(C)
Luc Bracoub
(L)
Marie-Yvonne Douste-Blazy
(MY)
Marie Dominique Fratacci
(MD)
Eric Vicaut
(E)
Shoichiro Sato
(S)
Kaori Miwa
(K)
Kyohei Fujita
(K)
Toshihiro Ide
(T)
Henry Ma
(H)
John Ly
(J)
Shaloo Singhal
(S)
Ronil Chandra
(R)
Lee-Anne Slater
(LA)
Cathy Soufan
(C)
Christopher Moran
(C)
Christopher Traenka
(C)
Sebastian Thilemann
(S)
Joachim Fladt
(J)
Henrik Gensicke
(H)
Leo Bonati
(L)
Beom Joon Kim
(BJ)
Moon-Ku Han
(MK)
Jihoon Kang
(J)
Eunbin Ko
(E)
Mi Hwa Yang
(MH)
Myung Suk Jang
(MS)
Sean Murphy
(S)
Fiona Carty
(F)
Layan Akijian
(L)
John Thornton
(J)
Mark Schembri
(M)
Elles Douven
(E)
Raquel Delgado-Mederos
(R)
Rebeca Marín
(R)
Pol Camps-Renom
(P)
Daniel Guisado-Alonso
(D)
Fidel Nuñez
(F)
Santiago Medrano-Martorell
(S)
Elisa Merino
(E)
Kotaro Iida
(K)
Syuhei Ikeda
(S)
Hiroyuki Irie
(H)
Derya Selcuk Demirelli
(DS)
Jayesh Modi Medanta
(JM)
Charlotte Zerna
(C)
Maria Valdés Hernández
(MV)
Paul Armitage
(P)
Anna Heye
(A)
Susana Muñoz-Maniega
(S)
Eleni Sakka
(E)
Michael Thrippleton
(M)
Martin Dennis
(M)
Ysoline Beigneux
(Y)
Mauro Silva
(M)
Narayanaswamy Venketasubramanian
(N)
Shu Leung Ho
(SL)
Raymond Tak Fai Cheung
(RTF)
Koon Ho Chan
(KH)
Kay Cheong Teo
(KC)
Edward Hui
(E)
Joseph Shiu Kwong Kwan
(JSK)
Richard Chang
(R)
Man Yu Tse
(MY)
Chu Peng Hoi
(CP)
Chung Yan Chan
(CY)
Oi Ling Chan
(OL)
Ryan Hoi Kit Cheung
(RHK)
Edmund Ka Ming Wong
(EKM)
Kam Tat Leung
(KT)
Suk Fung Tsang
(SF)
Hing Lung Ip
(HL)
Sze Ho Ma
(SH)
Karen Ma
(K)
Wing Chi Fong
(WC)
Siu Hung Li
(SH)
Richard Li
(R)
Ping Wing Ng
(PW)
Kwok Kui Wong
(KK)
Wenyan Liu
(W)
Lawrence Wong
(L)
Lino Ramos
(L)
Els De Schryver
(E)
Joost Jöbsis
(J)
Jaap van der Sande
(J)
Paul Brouwers
(P)
Yvo Roos
(Y)
Jan Stam
(J)
Stef Bakker
(S)
Henk Verbiest
(H)
Wouter Schoonewille
(W)
Cisca Linn
(C)
Leopold Hertzberger
(L)
Maarten van Gemert
(M)
Paul Berntsen
(P)
Dianne Van Dam-Nolen
(D)
M Eline Kooi
(ME)
Aad Van der Lugt
(A)
Peter Koudstaal
(P)
Alexander Leff
(A)
Nicholas Ward
(N)
Parashkev Nachev
(P)
Richard Perry
(R)
Hatice Ozkan
(H)
John Mitchell
(J)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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