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Safety of Dabigatran in Acute Ischemic Stroke Patients with Microbleeds: Post Hoc Analysis of DATAS-II Randomized Trial
Published online by Cambridge University Press: 30 January 2025
Abstract
Background:
Cerebral microbleeds are associated with an increased risk of hemorrhagic transformation (HT) following acute ischemic stroke. We investigated whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/transient ischemic attack (TIA) is modified by baseline microbleeds on MRI.
Methods:
The Dabigatran Treatment of Acute Stroke II trial randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. Microbleeds were centrally adjudicated in patients with an interpretable blood-sensitive sequence on baseline MRI. In this post hoc analysis, we used multivariable regression models to determine the association between microbleeds and any incident HT on day-30 MRI and excellent functional outcome (modified Rankin scale = 0–1) at 90 days.
Results:
A total of 251 (82.3%) participants (mean age = 66 ± 13 years, 36% women, median [IQR] onset-to-randomization time = 40[27–55] hours; median [IQR] NIHSS = 1 [0–2]) were included, of whom 82 (33%) had microbleeds. On day-30 MRI, 6% (n = 14) developed HT, and 80% (n = 191) achieved 90-day mRS of 0–1. We found no association between microbleed presence and HT (adjusted OR = 0.84; 95%CI:0.21–3.25) or excellent functional outcome (adjusted RR = 1.09; 95%CI:0.94–1.26). The rate of HT in patients with microbleeds was 3% with dabigatran and 4% with aspirin (OR = 0.85; 95%CI:0.11–6.75). Excellent functional outcome occurred in 74% and 84% of dabigatran and aspirin-treated patients, respectively (RR = 0.88; 95%CI:0.69–1.12). The presence, severity or location of microbleeds did not modify the effect of dabigatran on these outcomes (p-interaction > 0.05).
Conclusions:
Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.
Résumé
Innocuité du dabigatran chez des patients victimes d’un AVC ischémique aigu et présentant des microhémorragies : une analyse post-hoc de l’essai randomisé DATAS-II.
Les microhémorragies cérébrales sont associées à un risque accru de transformation hémorragique (TH) à la suite d’un AVC ischémique aigu. Nous avons ainsi cherché à savoir si l’effet du dabigatran (par opposition à l’aspirine) chez les patients victimes d’un AVC ischémique aigu mineur non cardio-embolique ou d’un accident ischémique transitoire (AIT) était modifié par la présence de microhémorragies observées lors d’examens d’IRM.
L’étude DATAS-II a rendu aléatoires les dossiers de 305 patients victimes d’un AVC ischémique aigu mineur non cardio-embolique ou d’un AIT en lien avec un traitement de dabigatran (150/110 mg deux fois par jour) et d’aspirine (81 mg par jour), et ce, pendant 30 jours. Les microhémorragies ont été évaluées de manière centralisée chez les patients présentant une séquence sensible aux produits sanguins interprétable lors d’examens d’IRM de base. Dans le cadre de cette analyse post-hoc, nous avons utilisé des modèles de régression multivariable pour déterminer l’association entre les microhémorragies et toute TH détectable à l’occasion d’examens d’IRM au trentième jour, ainsi qu’entre ces mêmes microhémorragies et un excellent résultat fonctionnel (score de Rankin modifiée ou SRM = 0-1) au bout de 90 jours.
Au total, 251 (82,3 %) participants (âge moyen = 66±13 ans ; 36 % de femmes ; délai médian [EI] entre les débuts des AVC et la randomisation = 40 [27-55] heures ; NIHSS médian [EI] = 1 [0-2]) ont été inclus, dont 82 (33 %) présentaient des microhémorragies. Lors d’examens d’IRM au trentième jour, 6 % des participants (n = 14) ont développé une TH et 80 % d’entre eux (n = 191) ont donné à voir un SRM de 0-1 au bout de 90 jours. Il est à noter que nous n’avons pas trouvé d’association entre la présence de microhémorragies et de TH (RC ajusté = 0,84 ; IC 95 % : 0,21-3,25) ou un excellent résultat au SRM (RR ajusté = 1,09 ; IC 95 % : 0,94-1,26). Le taux de TH chez les patients présentant des microhémorragies était par ailleurs de 3 % avec le dabigatran et de 4 % avec l’aspirine (RC = 0,85 ; IC 95 % : 0,11-6,75). Un excellent résultat au SRM a été respectivement obtenu chez 74 % et 84 % des patients traités au moyen du dabigatran et de l’aspirine (RR = 0,88 ; IC 95 % : 0,69-1,12). Enfin, la présence, la sévérité ou la localisation des microhémorragies n’ont pas modifié l’effet du dabigatran sur ces résultats (p-interaction > 0,05).
Un traitement précoce par le dabigatran semble sécuritaire chez les patients victimes d’un AVC ischémique aigu mineur non cardio-embolique ou d’un AIT et sujets à une maladie des petits vaisseaux cérébraux marquée par des microhémorragies observables lors d’examens d’IRM.
Keywords
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- Original Article
- Information
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- © The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation
Footnotes
Trial Registration: ClinicalTrials.gov; identifier: NCT02295826.
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Balali et al. supplementary material
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