Impact of type of oral anticoagulants in patients with cerebral microbleeds after atrial fibrillation-related ischemic stroke or TIA: Results of the NOACISP-LONGTERM registry

Benjamin Wagner; Lisa Hert; Alexandros A Polymeris; Sabine Schaedelin; Johanna M Lieb; David J Seiffge; Christopher Traenka; Sebastian Thilemann; Joachim Fladt; Valerian L Altersberger; Annaelle Zietz; Tolga D Dittrich; Urs Fisch; Henrik Gensicke; Gian Marco De Marchis; Leo H Bonati; Philippe A Lyrer; Stefan T Engelter; Nils Peters

doi:10.3389/fneur.2022.964723

Impact of type of oral anticoagulants in patients with cerebral microbleeds after atrial fibrillation-related ischemic stroke or TIA: Results of the NOACISP-LONGTERM registry

Front Neurol. 2022 Sep 20:13:964723. doi: 10.3389/fneur.2022.964723. eCollection 2022.

Authors

Benjamin Wagner¹, Lisa Hert^{1

2}, Alexandros A Polymeris¹, Sabine Schaedelin³, Johanna M Lieb⁴, David J Seiffge^{1

5}, Christopher Traenka^{1

6}, Sebastian Thilemann¹, Joachim Fladt¹, Valerian L Altersberger¹, Annaelle Zietz¹, Tolga D Dittrich¹, Urs Fisch¹, Henrik Gensicke^{1

6}, Gian Marco De Marchis¹, Leo H Bonati¹, Philippe A Lyrer¹, Stefan T Engelter^{1

6}, Nils Peters^{1

6

7}

Affiliations

¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
² Department of Intensive Care Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
³ Clinical Trial Unit, University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Department of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁶ Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter and Department of Clinical Research, University of Basel, Basel, Switzerland.
⁷ Stroke Center, Klinik Hirslanden Zurich, Zurich, Switzerland.

Abstract

Background: Cerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).

Methods: Observational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists [VKAs] vs. direct oral anticoagulants [DOACs]) with clinical outcome.

Results: Of 310 AF-stroke patients treated with OAC [DOACs: n = 234 (75%); VKAs: n = 76 (25%)], CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 [1.614; 8.277]; p = 0.002; DOACs: HR 2.230 [1.233; 4.034]; p = 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups [VKAs 13/20(65%) vs. DOACs 19/66(29%); p < 0.01]. The VKA-group had a 2-fold higher IS [VKAs:4 (20%) vs. DOACs:6 (9%); p = 0.35] and a 10-fold higher ICH rate [VKAs: 3 (15%) vs. DOACs: 1 (1.5%); p = 0.038]. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 [0.17; 0.94]; p = 0.04).

Conclusions: In AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.

Clinical trial registration: http://www.clinicaltrials.gov, Unique identifier: NCT03826927.

Keywords: anticoagulation; atrial fibrillation; cerebral microbleeds; direct-acting oral anticoagulant; small vessel disease; stroke; vitamin K anticoagulants.

Associated data

ClinicalTrials.gov/NCT03826927