Clinical presentation, diagnostic findings and management of cerebral ischemic events in patients on treatment with non-vitamin K antagonist oral anticoagulants – A systematic review

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower associated risk of intracranial hemorrhage compared to Vitamin K antagonists. Nevertheless, ischemic strokes also occur in patients who are being treated with NOAC. In those particular patients, knowledge about the underlying stroke etiology, clinical presentation, acute management, and complication rates is scarce. OBJECTIVE: Systematic literature review to provide a comprehensive clinical overview in terms of presentation, laboratory, imaging parameters and outcomes of patients suffering from acute cerebral ischemic events (i.e. TIA and acute ischemic stroke) while on treatment with a NOAC. Only if available, comparison to VKA is presented which was not the primary focus of this analysis. DATA SOURCES: PubMed/MEDLINE, Scopus and EMBASE from January 1, 2006, to November 20, 2018. STUDY ELIGIBILITY CRITERIA: 52 studies providing detailed information on a total of 12247 patients were included. We excluded case reports and case series with less than five patients. STUDY APPRAISAL AND SYNTHESIS METHOD: We systematically assessed study quality using a bias tool and pooled consistent data. RESULTS: Existing data indicates milder stroke severity and smaller infarct size of acute ischemic stroke on treatment with NOAC compared to stroke occurrence on Vitamin K antagonists (VKA). Established risk factors for ischemic events also play a role in stroke while on NOACs, albeit the underlying etiology remains poorly understood. Intravenous thrombolysis and endovascular therapy seem to be safe and effective, but patient selection for recanalization therapies is challenging. LIMITATIONS: Limited quality of published data, duplicate cases, statistical issues of data pooling, possible incomplete retrieval of identified research and reporting bias might have limited our findings. CONCLUSIONS: Acute ischemic events despite treatment with NOAC therapy are insufficiently investigated. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42018074853.