Abstract
Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept. At our hospital in Tampa, Florida, two octogenarians with atrial fibrillation, adherent with the DOAC dabigatran, presented with AIS shortly after symptom onset. Both received idarucizumab, then IVT. Clinical outcomes, treatment times, and perfusion-based neuroradiographic parameters were assessed. Patient A had a 41 ml penumbra on computed tomography perfusion (CTP) scan that decreased to 15 ml in final infarct volume on follow-up imaging, resulting in a 26 ml penumbral salvage (63.4%), and National Institutes of Health Stroke Scale (NIHSS) improved from 11 to 9 . Patient B had a 23 ml penumbra on CTP that decreased to 0.5 ml on follow-up imaging, resulting in a 22.5 ml penumbral salvage (97.8%), and NIHSS improved from 9 to 4. Neither developed bleeding complications. Both had delayed door-to-needle times but nevertheless demonstrated clinical neurological improvements.In our limited experience, IVT after immediate DOAC reversal in AIS patients on dabigatran was associated with clinical improvement in NIHSS by 2 to 5 points (with no neuroworsening), and penumbral salvage of ischemic brain tissue on neuroimaging ranging from 63.4% to 97.8%. Further reporting on this may lead to greater IVT use and better outcomes in “DOAC failures”, especially for patients without other acute treatment options such as mechanical thrombectomy. Research into other anticoagulant reversal agents pre-IVT in AIS is also warranted.
Highlights
Despite the clinical effectiveness of direct oral anticoagulants (DOAC) for patients with atrial fibrillation (AF), an acute ischemic stroke (AIS) may occur while anticoagulated anyway; this breakthrough event is given the general term, “DOAC failure.” In four landmark randomized trials, the “DOAC failure” rate was 1.1% for dabigatran, 1.7% for rivaroxaban, 1.3% for apixaban, and 1.2% for edoxaban [1,2,3,4]
Because these scenarios are not uncommon, the question is: what if an AF patient arrives at an emergency room with an AIS “within the window” for intravenous thrombolysis (IVT) but was adherent to their DOAC recently? The latest American Heart/Stroke Association (AHA/ASA) guidelines on this topic do not recommend IVT for patients who have taken their last DOAC within 48 hours [7]
Limitations of this report include the following: (1) Patient A underwent both IVT and mechanical thrombectomy (MT) which may have led to further clinical improvement than IVT alone, (2) different DOAC agents were started in the subacute phase after the acute strategy, and (3) at different times, which may have confounded hemorrhage risk at a follow-up visit, and (4) this report by itself on face value can only provide loose conclusions due to its size: we describe only two patients who underwent IVT after DOAC reversal
Summary
Despite the clinical effectiveness of direct oral anticoagulants (DOAC) for patients with atrial fibrillation (AF), an acute ischemic stroke (AIS) may occur while anticoagulated anyway; this breakthrough event is given the general term, “DOAC failure.” In four landmark randomized trials, the “DOAC failure” rate was 1.1% for dabigatran, 1.7% for rivaroxaban, 1.3% for apixaban, and 1.2% for edoxaban [1,2,3,4]. At our Comprehensive Stroke Center in Tampa, Florida, two right-handed octogenarians presented about a month apart with acute left hemiparesis within an IVT treatment window but with the contraindication of recent dabigatran use. We discussed with these patients and their families regarding both the AHA/ASA guidelines and the European experience, the lack of controlled trial data for the use of idarucizumab in this setting, and reviewed the risks and benefits of conventional IVT. An 83-year-old right-handed man with AF, hypertension, ischemic cardiomyopathy, and a defibrillator, presented 50 minutes after the acute onset of the subjective left arm and leg “heaviness” while driving Two weeks prior, he developed dark stools after starting colchicine for gout. MRI brain (below) revealed a final infarct volume of only 0.5 ml
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