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

Abstract

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.

Mechanical thrombectomy for acute ischaemic stroke during therapeutic anticoagulation: long-term outcomes

“…This study confirms the results of others [22,23], namely that MT is safe and efficacious in anticoagulated patients with AIS. However, systematic studies that include data on coagulation status and the decision-making procedure before MT, and comparing the various anticoagulation drugs in the context of acute stroke treatment, are necessary.…”

Is decreased stroke severity in patients with atrial fibrillation receiving non‐vitamin K oral anticoagulant treatment the coup de grâce for warfarin?

“…Observational data coupled with the findings of the meta‐analysis by Costello et al. suggest that NOACs are not only associated with lower stroke incidence but also with decreased stroke severity in patients with incident events while on treatment, thus providing further support to the current European Society of Cardiology guidelines recommending NOACs over warfarin for eligible patients with AF .…”

“…Observational study data suggest that patients with ICH under NOAC treatment tend to present with smaller hematoma volumes and less severe syndromes compared with patients with ICH under treatment with vitamin K antagonists (VKAs) . Likewise, existing observational evidence also suggests milder stroke severity and smaller infarct sizes for acute ischaemic stroke patients on NOAC treatment compared with those on treatment with VKAs . However, taking into account that previous reports also suggest decreased stroke severity – similar to NOACs –in patients on VKA treatment and international normalized ratio values within therapeutic range on admission , a potential interaction between stroke severity and impaired anticoagulation rather than drug regimen per se needs to be excluded before any firm conclusion on the superiority of NOACs for the prevention of severe strokes can be made with certainty.…”

Acute Stroke Treatment in an Anticoagulated Patient: When Is Thrombolysis an Option?

“…A recent (2014-2019) Swiss cohort study showed that 18% of all AF patients with ischemic stroke had been on prior VKA therapy and 20% on orior DOAC therapy [16••]. Reasons for ischemic stroke despite anticoagulation include competing stroke etiology or mechanisms (e.g., large-artery atherosclerosis, small-vessel disease, active malignancy [17][18][19][20][21], medication error (e.g., non-adherence, inappropriate DOAC dosage, or subtherapeutic INR) as well as cardioembolism despite anticoagulant therapy. However, recent studies found that prior therapeutic anticoagulation with VKA or DOAC was associated with lower stroke severity [16 Intravenous thrombolysis with alteplase is the gold standard in the treatment of acute ischemic stroke with significant improvement in functional outcome [23][24][25][26].…”