MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation

Abstract

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.

Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

“…Other studies have provided supportive observational evidence that incorporating small vessel disease markers, specifically CMB presence and WMH severity, can improve the performance of clinical risk scores for ICH 11,12 , and the current analysis suggests that incorporating BGPVS status into these scores might usefully be investigated. An advantage of BGPVS status as a marker might be that it can be quantified on axial T2 imaging, a routine component of nearly all clinical MRI brain imaging.…”

“…We wished to investigate this question in patients with atrial fibrillation taking oral anticoagulants (OAC) after ischaemic stroke or TIA. We hypothesized that BGPVS and CSOPVS would be associated with anticoagulant-related intracranial hemorrhage (OAC-ICH), independent of other A C C E P T E D markers of cerebral small vessel disease linked to OAC-ICH, notably CMBs and white matter hyperintensities 11,12 .…”

Long-Term Anticoagulation in Secondary Ischemic Stroke Prevention: The Prospective Multicenter RESTAIC Registry

“…Several registries have been published in recent years to study the use of the various oral anticoagulant treatments in stroke patients (18)(19)(20)(21)(22)(23)(24)(25)(26), mainly evaluating clinical outcomes such as stroke recurrence, cerebral hemorrhage, or functional outcome. Other published registries were focused on the use of radiological markers such as cerebral microbleeds or white matter hyperintensities in order to stratify the hemorrhagic risk in this specific population (27,28). Also, individual patient data analysis of seven prospective cohort studies has been recently published addressing the outcomes in patients with AF who received anticoagulation treatment in secondary prevention after stroke (29).…”

Predicting Who Will Experience Cerebral Hemorrhage When Anticoagulated

“…Independent of making the diagnosis of CAA, certain features on brain MRI can point to increased risk of hemorrhage with anticoagulation, including the presence of cerebral microbleeds, moderateto-severe leukoaraiosis, and, likely, superficial siderosis (Table). 8 The predictive utility of brain MRI may be augmented by the incorporation of apolipoprotein E genotype status. 9 The APOE ε2 and ε4 alleles have been shown to increase risk of lobar hemorrhage in many populations.…”