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. Issue 4 (April 2021)

• Record Type: Journal Article
• Authors: 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; 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; Harkness, Kirsty; Shaw, Louise; Sword, Jane; Mohd Nor, Azlisham; Sharma, Pankaj; Kelly, Deborah; Harrington, Frances; Randall, Marc; Smith, Matthew; Mahawish, Karim; Elmarim, Abduelbaset; Esisi, Bernard; Cullen, Claire; Nallasivam, Arumug; Price, Christopher; Barry, Adrian; Roffe, Christine; Coyle, John; Hassan, Ahamad; Birns, Jonathan; Cohen, David; Sekaran, Lakshmanan; Parry-Jones, Adrian; Parry, Anthea; Hargroves, David; Proschel, Harald; Datta, Prabel; Darawil, Khaled; Manoj, Aravindakshan; Burn, Mathew; Patterson, Chris; Giallombardo, Elio; Smyth, Nigel; Mansoor, Syed; Anwar, Ijaz; Marsh, Rachel; Ispoglou, Sissi; Chadha, Dinesh; Prabhakaran, Mathuri; Meenakishundaram, Sanjeevikumar; O'Connell, Janice; Scott, Jon; Krishnamurthy, Vinodh; Aghoram, Prasanna; McCormick, Michael; Sprigg, Nikola; O'Mahony, Paul; Cooper, Martin; Choy, Lillian; Wilkinson, Peter; Leach, Simon; Caine, Sarah; Burger, Ilse; Gunathilagan, Gunaratam; Guyler, Paul; Emsley, Hedley; Davis, Michelle; Manawadu, Dulka; Pasco, Kath; Mamun, Maam; Luder, Robert; Sajid, Mahmud; Anwar, Ijaz; Okwera, James; Warburton, Elizabeth; Saastamoinen, Kari; England, Timothy; Putterill, Janet; Flossman, Enrico; Power, Michael; Dani, Krishna; Mangion, David; Suman, Appu; Corrigan, John; Lawrence, Enas; Vahidassr, Djamil; Shakeshaft, Clare; Brown, Martin; Charidimou, Andreas; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark; Yousry, Tarek; Harkness, Kirsty; Flossmann, Enrico; Smyth, Nigel; Shaw, Louise; Warburton, Elizabeth; Muir, Keith; Gratz, Pascal; Mattle, Heinrich; Panos, Leonidas; Korczyn, Amos; Kliper, Efrat; Maeder, Philippe; Gass, Achim; Pachai, Chahin; Bracoub, Luc; Douste-Blazy, Marie-Yvonne; Fratacci, Marie Dominique; Vicaut, Eric; Sato, Shoichiro; Miwa, Kaori; Fujita, Kyohei; Ide, Toshihiro; Ma, Henry; Ly, John; Singhal, Shaloo; Chandra, Ronil; Slater, Lee-Anne; Soufan, Cathy; Moran, Christopher; Traenka, Christopher; Thilemann, Sebastian; Fladt, Joachim; Gensicke, Henrik; Bonati, Leo; Kim, Beom Joon; Han, Moon-Ku; Kang, Jihoon; Ko, Eunbin; Yang, Mi Hwa; Jang, Myung Suk; Murphy, Sean; Carty, Fiona; Akijian, Layan; Thornton, John; Schembri, Mark; Douven, Elles; Delgado-Mederos, Raquel; Marín, Rebeca; Camps-Renom, Pol; Guisado-Alonso, Daniel; Nuñez, Fidel; Medrano-Martorell, Santiago; Merino, Elisa; Iida, Kotaro; Ikeda, Syuhei; Irie, Hiroyuki; Demirelli, Derya Selcuk; Medanta, Jayesh Modi; Zerna, Charlotte; Hernández, Maria Valdés; Armitage, Paul; Heye, Anna; Muñoz-Maniega, Susana; Sakka, Eleni; Thrippleton, Michael; Dennis, Martin; Beigneux, Ysoline; Silva, Mauro; Venketasubramanian, Narayanaswamy; Ho, Shu Leung; Cheung, Raymond Tak Fai; Chan, Koon Ho; Teo, Kay Cheong; Hui, Edward; Kwan, Joseph Shiu Kwong; Chang, Richard; Tse, Man Yu; Hoi, Chu Peng; Chan, Chung Yan; Chan, Oi Ling; Cheung, Ryan Hoi Kit; Wong, Edmund Ka Ming; Leung, Kam Tat; Tsang, Suk Fung; Ip, Hing Lung; Ma, Sze Ho; Ma, Karen; Fong, Wing Chi; Li, Siu Hung; Li, Richard; Ng, Ping Wing; Wong, Kwok Kui; Liu, Wenyan; Wong, Lawrence; Ramos, Lino; De Schryver, Els; Jöbsis, Joost; van der Sande, Jaap; Brouwers, Paul; Roos, Yvo; Stam, Jan; Bakker, Stef; Verbiest, Henk; Schoonewille, Wouter; Linn, Cisca; Hertzberger, Leopold; van Gemert, Maarten; Berntsen, Paul; Van Dam-Nolen, Dianne; Kooi, M Eline; Van der Lugt, Aad; Koudstaal, Peter; Leff, Alexander; Ward, Nicholas; Nachev, Parashkev; Perry, Richard; Ozkan, Hatice; Mitchell, John;
• Is Part Of: Lancet neurology. Volume 20:Issue 4(2021)
• Page Start: 294
• Page End: 303
• Publication Date: 2021-04
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Nervous System Diseases -- Periodicals; Neurologie -- Périodiques; Neurology; Electronic journals; Periodicals; 616.805
• DOI: 10.1016/S1474-4422(21)00024-7
• Languages: English
• ISSNs: 1474-4422

Abstract

Summary: 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.