Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation
Authors: Soo Yannie , Zietz Annaelle , Yiu Brian , Mok Vincent C. T. , Polymeris Alexandros A. , Seiffge David , Ambler Gareth , Wilson Duncan , Leung Thomas Wai Hong , Tsang Suk Fung , Chu Winnie , Abrigo Jill , Cheng Cyrus , Lee Keon‐Joo , Lim Jae‐Sung , Shiozawa Masayuki , Koga Masatoshi , Chabriat Hugues , Hennerici Michael , Wong Yuen Kwun , Mak Henry , Collet Roger , Inamura Shigeru , Yoshifuji Kazuhisa , Arsava Ethem Murat , Horstmann Solveig , Purrucker Jan , Lam Bonnie Y. K. , Wong Adrian , Kim Young Dae , Song Tae‐Jin , Lemmens Robin , Eppinger Sebastian , Gattringer Thomas , Uysal Ender , Demirelli Derya Selçuk , Bornstein Natan M. , Assayag Einor Ben , Hallevi Hen , Molad Jeremy , Nishihara Masashi , Tanaka Jun , Coutts Shelagh B. , Kappelle L. Jaap , Al‐Shahi Salman Rustam , Jager Rolf , Lip Gregory Y. H. , Goeldlin Martina B. , Panos Leonidas D. , Mas Jean‐Louis , Legrand Laurence , Karayiannis Chris , Phan Thanh , Bellut Maximilian , Chappell Francesca , Makin Stephen , Hayden Derek , Williams David , van Dam‐Nolen Dianne H. K. , Nederkoorn Paul J. , Barbato Carmen , Browning Simone , Wiegertjes Kim , Tuladhar Anil Man , Mendyk Anne‐Marie , Köhler Sebastian , van Oostenburgge Robert , Zhou Ying , Xu Chao , Hilal Saima , Gyanwali Bibek , Chen Christopher , Lou Min , Staals Julie , Bordet Regis , Kandiah Nagaendran , de Leeuw Frank‐Erik , Simister Robert , Hendrikse Jeroen , Wardlaw Joanna , Kelly Peter , Fluri Felix , Srikanth Velandai , Calvet David , Jung Simon , Kwa Vincent, I. H. , Smith Eric E. , Hara Hideo , Yakushiji Yusuke , Orken Dilek Necioglu , Fazekas Franz , Thijs Vincent , Heo Ji‐Hoe , Veltkamp Roland , Ay Hakan , Imaizumi Toshio , Lau Kui Kai , Jouvent Eric , Toyoda Kazunori , Yoshimura Sohei , Bae Hee‐Joon , Martí‐Fàbregas Joan , Prats‐Sánchez Luis , Lyrer Philippe , Best Jonathan , Werring David , Engelter Stefan T. , Peters Nils ,   the Microbleeds International Collaborative Network
Published: March 2023

Objectives

Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet).

Methods

We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use.

Results

A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76–4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04–1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient‐years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient‐years).

Interpretation

Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high‐risk group. ANN NEUROL 2023;94:61–74