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. 2024 Dec;9(4):959-967.
doi: 10.1177/23969873241252751. Epub 2024 May 13.

Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines

Philipp Bücke  1 , Simon Jung  1 , Johannes Kaesmacher  2 , Martina B Goeldlin  1 , Thomas Horvath  1 , Ulrike Prange  1 , Morin Beyeler  1   3 , Urs Fischer  1   4 , Marcel Arnold  1 , David J Seiffge  1 , Thomas R Meinel  1
Affiliations

Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines

Philipp Bücke et al. Eur Stroke J. 2024 Dec.

Abstract

Introduction: This study aimed to report the safety and efficacy of off-label intravenous thrombolysis (IVT) with alteplase after sequentially liberalizing our institutional guidelines allowing IVT for patients under direct oral anticoagulants (DOACs) regardless of plasma levels, time of last intake, and without prior anticoagulation reversal therapy.

Patients and methods: We utilized the target-trial methodology to emulate hypothetical criteria of a randomized controlled trial in our prospective stroke registry. Consecutive DOAC patients (06/2021-11/2023) otherwise qualifying for IVT were included. Safety and efficacy outcomes (symptomatic intracranial hemorrhage [ICH], any radiological ICH, major bleeding, 90-day mortality, 90-day good functional outcome [mRS 0-2 or return to baseline]) were assessed using inverse-probability-weighted regression-adjustment comparing patients with versus without IVT.

Results: Ninety eight patients fulfilled the target-trial criteria. IVT was given in 49/98 (50%) patients at a median of 178 (interquartile range 134-285) min after symptom onset with median DOAC plasma level of 77 ng/ml (15 patients had plasma levels > 100 ng/ml; 25/49 [51%] were treated within 12 h after last DOAC ingestion). Endovascular therapy was more frequent in patients without IVT (73% vs 33%). Symptomatic ICH occurred in 0/49 patients receiving IVT and 2/49 patients without IVT (adjusted difference -2.5%; 95% CI -5.9 to 0.8). The rates of any radiological ICH were comparable. Patients receiving IVT were more likely to have good functional outcomes.

Discussion and conclusion: After liberalizing our approach for IVT regardless of recent DOAC intake, we did not experience any safety concerns. The association of IVT with better functional outcomes warrants prospective randomized controlled trials.

Keywords: anticoagulants; atrial fibrillation; stroke; therapeutic thrombolysis.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MBG reports grants from the Bangerter-Rhyner-Foundation, Swiss Stroke Society, European Stroke Organisation, European Academy of Neurology and Insel Gruppe AG (all outside the submitted work). MA reports speaker honoraria from Astra Zeneca, Bayer, Covidien, Medtronic, Sanofi and honoraria for scientific advisory boards from Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, Pfizer, and research funding from the Swiss National Science Foundation (SNSF), and the Swiss Heart Foundation (SHF). UF reports financial support for the SWIFT DIRECT trial (Medtronic), research grants from Medtronic BEYOND SWIFT registry, SNSF, SHF, consulting fees from Medtronic, Stryker and CSL Behring (fees paid to institution); membership of a Data Safety Monitoring Board for the IN EXTREMIS trial and TITAN trial and Portola (Alexion) Advisory board (fees paid to institution). DS is on the advisory board of Bayer Switzerland AG and Portola/Alexion. He reports research funding from SNSF, SHF, Bangerter-Rhyner Foundation, Bayer Foundation, and Portola/Alexion. TRM reports grants from the Bangerter-Rhyner Foundation, the Baasch-Medicus Foundation, the University of Bern, the Swiss National Science Foundation and the Swiss Heart Foundation. All other authors report no competing interests.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Yearly distribution (2015–2022) of the spectrum of preceding anticoagulation in: (a) all code stroke patients and (b) those with a minimum NIHSS of 4 points at our comprehensive stroke center. Note the overall decrease in patients without anticoagulation. This is due to an increase of patients on DOACs since patients on VKA were also declining over time. Patients with parenteral anticoagulation (heparins) represent a minority of all patients on anticoagulation. DOAC: direct oral anticoagulants; VKA: vitamin-K antagonists.
Figure 2.
Figure 2.
Study flowchart.
See this image and copyright information in PMC

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