Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia
Authors: Du Houwei , Wilson Duncan , Ambler Gareth , Banerjee Gargi , Shakeshaft Clare , Cohen Hannah , Yousry Tarek , Al-Shahi Salman Rustam , Lip Gregory Y.H. , Houlden Henry , Brown Martin M. , Muir Keith W. , Jäger Hans Rolf , Werring David J. , Parry-Jones Adrian , Patterson Chris , Price Christopher , Elmarimi Abduelbaset , Parry Anthea , Nallasivam Arumug , Mohd Nor Azlisham , Esisi Bernard , Bruce David , Bhaskaran Biju , Roffe Christine , Cullen Claire , Holmes Clare , Cohen David , Hargroves David , Mangion David , Chadha Dinesh , Vahidassr Djamil , Manawadu Dulka , Giallombardo Elio , Warburton Elizabeth , Flossman Enrico , Gunathilagan Gunaratam , Proschel Harald , Emsley Hedley , Anwar Ijaz , Burger Ilse , Okwera James , Putterill Janet , O’Connell Janice , Bamford John , Corrigan John , Scott Jon , Birns Jonathan , Kee Karen , Saastamoinen Kari , Pasco Kath , Dani Krishna , Sekaran Lakshmanan , Choy Lillian , Iveson Liz , Mamun Maam , Sajid Mahmud , Cooper Martin , Burn Mathew , Smith Matthew , Power Michael , Davis Michelle , Smyth Nigel , Veltkamp Roland , Sharma Pankaj , Guyler Paul , O’Mahony Paul , Wilkinson Peter , Datta Prabel , Aghoram Prasanna , Marsh Rachel , Luder Robert , Meenakishundaram Sanjeevikumar , Subramonian Santhosh , Leach Simon , Ispoglou Sissi , Andole Sreeman , England Timothy , Manoj Aravindakshan , Frances Harrington , Rehman Habib , Sword Jane , Staals Julie , Mahawish Karim , Harkness Kirsty , Shaw Louise , McCormick Michael , Sprigg Nikola , Mansoor Syed , Krishnamurthy Vinodh 
Published: December 2020

Background and Purpose:
The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack.

Methods:
We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score.

Results:

We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD (
P
=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01–3.53];
P
=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04–1.70];
P
=0.023).

Conclusions:
In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02513316.