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Abstract
Objective We 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.
Methods Patients 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.
Results We 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).
Conclusion Patients 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 identifier NCT02238470.
Glossary
- AF=
- atrial fibrillation;
- CAA=
- cerebral amyloid angiopathy;
- CHA=
- cerebral hypertensive angiopathy;
- CHA2DS2-VASc=
- congestive heart failure (or left ventricular systolic dysfunction), hypertension: blood pressure consistently above 140/90 mm Hg (or treated hypertension on medication), age ≥75 years, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease (e.g., peripheral artery disease, myocardial infarction, aortic plaque), age 65–74 years, sex category (i.e., female sex);
- CI=
- confidence interval;
- CROMIS-2=
- Clinical Relevance of Microbleeds in Stroke–2;
- cSS=
- cortical superficial siderosis;
- DOAC=
- direct oral anticoagulant;
- FLAIR=
- fluid-attenuated inversion recovery;
- GRE=
- gradient-recalled echo;
- HAS-BLED=
- hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol;
- HERO=
- Hemorrhage Predicted by Resonance in Patients Receiving Oral Anticoagulants;
- HR=
- hazard ratio;
- ICH=
- intracranial hemorrhage;
- INR=
- international normalized ratio;
- MB=
- microbleed;
- OA=
- oral anticoagulant;
- SS=
- superficial siderosis;
- SWI=
- susceptibility-weighted imaging;
- VKA=
- vitamin K antagonist;
- WMH=
- white matter hyperintensity;
- WML=
- white matter lesion
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
HERO coinvestigators are listed in appendix 2.
Editorial, page 981
- Received August 25, 2018.
- Accepted in final form January 24, 2019.
- © 2019 American Academy of Neurology
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- Author response: MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation
- Reader response: MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation
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