Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase—Reply

Kam, Wayneho; Xian, Ying

doi:10.1001/jama.2022.6353

JAMA

2022

DOI: 10.1001/jama.2022.6353

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Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase—Reply

Wayneho Kam

Ying Xian

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Cited by 6 publications

(17 citation statements)

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“…Based on the findings reported by Kam et al, is it possible to provide a definite answer to the question of whether the use of alteplase is safe for patients with acute ischemic stroke and recent NOAC intake? Given some of the study limitations and caveats related to interpretation, several important questions remain.…”

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confidence: 99%

“…Given some of the study limitations and caveats related to interpretation, several important questions remain. First, in the study by Kam et al, the exact timing of the last NOAC dose was unknown. In contrast to anticoagulation with vitamin K antagonists, the anticoagulant effect of NOAC therapy is short and rapidly decreases within hours after intake .…”

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confidence: 99%

“…Kam et al tried to overcome this limitation by linking their data with a second registry (Addressing Real-world Anticoagulant Management Issues in Stroke) in which more granular information about NOAC therapy and last dose were recorded. However, the number of patients with available information was small (47 of 2207) and only 8 patients had their last NOAC dose within 24 hours and only 25 patients within 48 hours.…”

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confidence: 99%

“…Experienced stroke centers worldwide are using alteplase for patients who have taken NOAC therapy within 48 hours by applying different approaches and selection criteria, including therapy guided by NOAC plasma level concentration and reversal of NOAC treatment using the specific reversal agents idarucizumab and andexanet alfa. Kam et al did not provide information about whether any of these approaches had been used. Therefore, it remains unclear whether additional selection criteria for patients with prior NOAC use are needed, and if so, which may be best.…”

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confidence: 99%

“…The study of Kam et al in this issue of JAMA provides important evidence regarding the use of alteplase among patients with ischemic stroke taking prior NOAC therapy, although the findings to do not provide a definitive answer to the question of safety. Future studies are needed to provide more detailed data on patients with recent, verified NOAC intake within 48 hours of alteplase use and to assess the safety profile associated with different patient selection criteria.…”

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confidence: 99%

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Intravenous Thrombolytic Therapy for Treatment of Acute Ischemic Stroke in Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants

Seiffge

2022

JAMA

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confidence: 99%

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confidence: 99%

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confidence: 99%

See 3 more Smart Citations

Intravenous Thrombolytic Therapy for Treatment of Acute Ischemic Stroke in Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants

Seiffge

2022

JAMA

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Building Evidence on Safety of Thrombolysis for Patients Undergoing Direct Oral Anticoagulant Treatment

Mistry

2023

JAMA Neurol

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Nearly 20% of patients with acute ischemic stroke (AIS) are undergoing direct oral anticoagulant (DOAC) treatment at the time of their stroke. 1 Common indications for DOACs among these patients include stroke prevention from atrial fibrillation, treatment of venous and pulmonary thrombosis, and coronary and peripheral atherosclerotic disease. Novel indications for DOAC use are expected to emerge and may increase the proportion of patients with AIS who are undergoing treatment with DOACs. Current US and European acute stroke treatment guidelines recommend withholding intravenous thrombolysis (thrombolysis), a morbidity-and mortality-saving AIS treatment for patients with recent a DOAC use. 2,3 DOACs have emerged as preferred anticoagulants over vitamin K antagonists due to a favorable safety profile, particularly a lower risk of severe systemic and intracranial hemorrhage (ICH). 4 However, if this translates into a lower risk of hemorrhagic complications of thrombolysis for AIS in the setting of DOAC treatment is yet to be definitively determined as data supporting this practice are limited and heterogenous. The present study by Meinel et al 5 meaningfully advances the field by generating these critical data. Comparative analyses of different patient selection paradigms for thrombolysis in the presence of DOACs provide additional, timely relevance to the study.In this international, multicenter, observational, retrospective analysis of individual patient data from 64 centers, the authors included 832 patients with AIS undergoing intravenous thrombolysis who had ingested a DOAC agent within 48 hours of hospital arrival. Additionally, 32 375 control patients who had received intravenous thrombolysis without prior anticoagulation treatment (defined as having a therapeutic international normalized ratio with vitamin K antagonists or known DOAC treatment) were included for comparison. A priori calculation of the sample size required to detect differences in the primary outcome was not performed. Compared to the control population, patients with recent DOAC ingestion were older and had more comorbidities. They were more likely to have a large vessel occlusion but also had a higher rate of endovascular treatment (62% vs 55%). Dabigatran was the most frequently used DOAC (n = 342, 41%), followed by rivaroxaban (n = 258, 31%) and apixaban (n = 163, 20%). In terms of patient selection strategies used for thrombolysis, DOAC reversal was performed using idarucizumab among 252 patients (30%) receiving dabigatran (no other reversal agents were used among patients receiving other DOACs), 225 patients (27%) had DOAC plasma levels measured, and the remaining 355 patients (43%) had neither plasma drug levels or DOAC re-

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Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants

et al. 2023

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ImportanceInternational guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC).ObjectiveTo determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion.Design, Setting, and ParticipantsThis international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021.ExposuresPrior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation.Main Outcomes and MeasuresThe main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses.ResultsOf 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion.Conclusions and RelevanceIn this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

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Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase—Reply

Cited by 6 publications

References 4 publications

Intravenous Thrombolytic Therapy for Treatment of Acute Ischemic Stroke in Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants

Intravenous Thrombolytic Therapy for Treatment of Acute Ischemic Stroke in Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants

Building Evidence on Safety of Thrombolysis for Patients Undergoing Direct Oral Anticoagulant Treatment

Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants

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