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. 2024 Aug 1;81(8):805-813.
doi: 10.1001/jamaneurol.2024.1892.

Recurrent Ischemic Stroke in Patients With Atrial Fibrillation While Receiving Oral Anticoagulants

Mette Foldager Hindsholm  1   2 , Luis Alberto García Rodríguez  3 , Axel Brandes  4   5 , Jesper Hallas  6 , Birgit Bjerre Høyer  7 , Sören Möller  7   8 , Mahmut Edip Gurol  9 , Claus Ziegler Simonsen  1   2 , David Gaist  10
Affiliations

Recurrent Ischemic Stroke in Patients With Atrial Fibrillation While Receiving Oral Anticoagulants

Mette Foldager Hindsholm et al. JAMA Neurol. .

Abstract

Importance: Patients with atrial fibrillation (AF) can have an ischemic stroke (IS) despite oral anticoagulant (OAC) treatment. Knowledge regarding the association between OAC discontinuation and the subsequent risk of recurrent IS in patients with AF is limited.

Objectives: To determine the risk of recurrent IS in patients with AF receiving OAC and to evaluate the association between OAC discontinuation and the risk of recurrent IS.

Design, setting, and participants: This is a nationwide cohort study of patients aged 50 years or older in Denmark who had AF and an IS (entry IS) and were initiating or restarting subsequent OAC treatment after being discharged between January 2014 and December 2021. Patients were followed up for recurrent IS until June 2022. Within this study cohort, a nested case-control analysis was performed in which patients with recurrent IS were matched to patients receiving OAC who had not yet experienced a stroke. Data were analyzed from May 25, 2023, to April 18, 2024.

Exposure: Use of OAC at the time of recurrent IS or the equivalent date in matched controls based on redeemed prescriptions.

Main outcomes and measures: The primary outcome was recurrent IS. Crude and adjusted cumulative incidences of recurrent IS and all-cause mortality were calculated in cohort analyses, and adjusted odds ratios (aORs) were determined for recurrent IS associated with OAC discontinuation in nested case-control analyses.

Results: The study cohort included 8119 patients (4392 [54.1%] male; mean [SD] age, 78.4 [9.6] years; median (IQR) CHA2DS2-VASc score, 4.0 [3.0-5.0]). Over a mean (SD) follow-up of 2.9 (2.2) years, 663 patients had a recurrent IS, of whom 533 (80.4%) were receiving OAC at the time of their recurrent IS. The crude cumulative incidence of recurrent IS at 1 year was 4.3% (95% CI, 5.9%-7.1%), and the crude cumulative incidence of all-cause mortality was 15.4% (95% CI, 14.7%-16.2%). Adjusted analysis showed similar results. Patients who discontinued OACs had a higher risk of recurrent IS (89 cases [13.4%], 180 controls [6.8%]; aOR, 2.13; 95% CI, 1.57-2.89) compared with patients still receiving OAC.

Conclusions and relevance: The risks of recurrent IS and mortality were high in patients with AF despite secondary prevention with OAC, and OAC discontinuation doubled the risk of recurrent IS compared with patients who continued OAC. This finding highlights the importance of OAC continuation and the need for improved secondary stroke prevention in patients with AF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hindsholm reported grants from C. B. Holding, Aarhus during the conduct of the study. Dr García Rodríguez reported grants from Bayer outside the submitted work. Dr Brandes reported personal fees from Bristol Myers Squibb and grants from Theravance, Zealand Region, Canadian Institutes of Health Research, Danish Heart Foundation, European Union Interreg 5A Programme, and Independent Research Fund Denmark outside the submitted work. Dr Hallas reported grants from Astellas, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Servier, and LEO Pharma outside the submitted work. Dr Gurol reported grants from Avid, Pfizer, Boston Scientific, and the National Institutes of Health outside the submitted work. Dr Simonsen reported grants from Health Research Foundation of Central Denmark Region during the conduct of the study; and personal fees from Pfizer outside the submitted work. Dr Gaist reported personal fees from Pfizer and Bristol Myers Squibb and grants from Bayer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
Exclusions were performed stepwise in the order presented. AF indicates atrial fibrillation; IS, ischemic stroke; OAC, oral anticoagulant.
Figure 2.
Figure 2.. Cumulative Incidence of Recurrent Ischemic Stroke (IS) and All-Cause Mortality Within the First 2 Years of Follow-Up
Cumulative incidence of recurrent IS (A) and all-cause mortality (B) are shown for the study cohort (N = 8119) within the first 2 years of follow-up.
See this image and copyright information in PMC

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