Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non–Vitamin K Antagonist Oral Anticoagulants Preceding Stroke

Abstract

Background and Purpose— Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods— A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results— We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5–14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0–2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12–2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08–1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45–14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions— These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

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

“…Seiffge et al estimated that IVT could be used in more than half of patients with prior rivaroxaban treatment with about 28% of patients denied by current guidelines [30,45,81]. Recent analyses concluded that IVT is probably effective and safe in select AIS patients undergoing NOAC treatment [81–84]. However, optimal patient selection is dependent on coagulation parameters that have not yet been sufficiently evaluated, and the variable selection criteria used in available studies do not allow for a consensus [39,42,85,86].…”

“…Initial reports on successful and safe IVT after idarucizumab administration are promising, but limited experience does not allow for a final statement on the safety of IVT after antagonization [33,84]. Additionally, it is not clear whether idarucizumab/IVT should be administered in every dabigatran patient with an AIS or only if direct EVT is not possible.…”

Immediate Reversal of Dabigatran by Idarucizumab Prior to Laboratory and Imaging Results in Acute Stroke

“…Even if limited on anecdotal experiences of case reports and series this review provides further evidence that patients taking NOACs in general might not have an increased bleeding risk upon intravenous thrombolysis. With respect to dabigatran only, authors found, that patients treated with idarucizumab were significantly more likely to have favorable outcomes and are numerically less likely to bleed and die ( 19 ). The here presented case is another one without hemorrhagic complication.…”

Off-label use of intravenous thrombolysis for acute ischemic stroke: a critical appraisal of randomized and real-world evidence

“… 63 Similarly, a literature review documented rates of sICH following IVT of 4.3% in selected AIS patients pre-treated with NOACs, despite a median time interval from the last dose of the anticoagulant to IVT of only 8 h. Moreover, the administration of idarucizumab before IVT in 44 dabigatran pre-treated patients resulted in numerically fewer sICHs (4.5% versus 7.4%) and deaths (4.5% versus 12.0%). 64 Although both reviews conclude that in selected patients with NOAC pre-treatment IVT may not increase sICH, more data are needed to clarify the safety of IVT in this group of patients, particularly when specific coagulation assays to assess residual anticoagulant activity at patient presentation are not available.…”