Mechanisms of ischaemic strokes and transient ischaemic attacks despite oral anticoagulation in patients with atrial fibrillation

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Atrial fibrillation with breakthrough ischaemic stroke or TIA (n=179). Intervention: Good anticoagulant control vs. Suboptimal anticoagulant control. Primary outcome: Non-cardioembolic mechanism of ischaemic stroke or TIA (aOR 3.67, 95% CI 1.35-9.99, p=0.011).

Q: What does this research mean for the field?

Good anticoagulant control is independently associated with higher odds of a non-cardioembolic mechanism (aOR 3.67) among atrial fibrillation patients presenting with breakthrough ischemic stroke or TIA. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Karim Mahawish; Valery Feigin; Rita Krishnamurthi; Harvey White

doi:10.26635/6965.7380

June 9, 2026New Zealand Medical Journal

Mechanisms of ischaemic strokes and transient ischaemic attacks despite oral anticoagulation in patients with atrial fibrillation

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Key result

Good anticoagulant control in AF is linked to ~267% higher odds of non-cardioembolic breakthrough stroke.

aOR 3.67
95% CI 1.35-9.99
P=0.011
n=179

Why the study?

The study aimed to characterise the mechanisms underlying breakthrough ischaemic stroke or transient ischaemic attack despite oral anticoagulation in patients with atrial fibrillation.

Is good anticoagulant control associated with a non-cardioembolic mechanism of breakthrough ischemic stroke or TIA in patients with atrial fibrillation?

Key Points

To characterise the mechanisms underlying breakthrough ischaemic stroke or transient ischaemic attack despite oral anticoagulation in patients with atrial fibrillation.
Conducted a cross-sectional analysis of 179 adults (76/179 [43%] female) with non-valvular atrial fibrillation presenting with ischaemic stroke (130/179 [73%]) or transient ischaemic attack (49/179 [27%]) in the ARCOS V study in Auckland, New Zealand (September 2020 to August 2021).
Assessed anticoagulant adherence (good control defined as proportion of days covered ≥80% for direct oral anticoagulants or time in therapeutic range ≥70% for warfarin; median observation window 149 days) and adjudicated event mechanism using standardised TOAST criteria.
Cardioembolic etiology accounted for 138/179 events (77%) and was associated with lower rates of good anticoagulant control (87/138 [63%] vs 34/41 [83%], p=0.017) and higher rates of peri-event under-exposure or missed dosing (90/138 [65%] vs 18/41 [44%], p=0.014) compared with non-cardioembolic events.
In multivariable logistic regression, good anticoagulant control was independently associated with higher odds of a non-cardioembolic mechanism (adjusted odds ratio 3.67, 95% CI 1.35–9.99, p=0.011), while body mass index was inversely associated (adjusted odds ratio 0.94, 95% CI 0.88–0.99, p=0.037).

Study Design

Type

Cross-Sectional (n=179)

Structured PICO

Is good anticoagulant control associated with a non-cardioembolic mechanism of breakthrough ischemic stroke or TIA in patients with atrial fibrillation?

P

Population

179 adults with non-valvular atrial fibrillation who experienced an ischemic stroke or transient ischemic attack despite oral anticoagulation, identified from a regional population-based registry.

E

Exposure

Good anticoagulant control (proportion of days covered ≥80% for DOACs or time in therapeutic range ≥70% for warfarin)

C

Comparator

Poor anticoagulant control or peri-event missed/under-dosing

O

Outcome

Mechanism of ischemic stroke or TIA (cardioembolic vs non-cardioembolic)

Main Result

Odds Ratio: 3.67 (95% CI 1.35–9.99)

p-value: p=0.011

Breakthrough ischemic strokes in atrial fibrillation patients on oral anticoagulation are predominantly driven by anticoagulant under-exposure or competing non-cardioembolic mechanisms rather than true anticoagulant failure.

Limitations

Retrospective assessment of anticoagulant exposure with potential for residual confounding
Absence of a contemporaneous control group
Imperfect laboratory assessment of DOAC exposure, particularly for factor Xa inhibitors
Potential for type I error inflation due to multiple statistical testing
Modest sample size may lead to type II errors for non-significant findings

Implication

Good anticoagulant control may unmask non-cardioembolic stroke mechanisms in AF; hypothesis-generating and should not yet change practice.

Abstract

AIMS: The aim of this article was to characterise the mechanisms underlying "breakthrough" ischaemic stroke (IS) or transient ischaemic attack (TIA) despite oral anticoagulation in patients with atrial fibrillation (AF). METHODS: We conducted a cross-sectional analysis of adults with non-valvular AF who experienced IS/TIA in the fifth Auckland Regional Community Stroke Study (ARCOS V: September 2020 to August 2021). Using clinical records, we collected data on demographics, comorbidities and peri-event anticoagulant dosing and intake. Anticoagulant adherence in the months preceding IS/TIA was categorised as good control if proportion of days covered (PDC) ≥80% for direct oral anticoagulant users or time in therapeutic range (TTR) ≥70% for warfarin users. IS/TIA mechanism was adjudicated using standardised criteria and classified as cardioembolic or non-cardioembolic, and patient characteristics were compared. RESULTS: Among 179 patients (76/179 [43%] female), 138/179 events (77%) were adjudicated as cardioembolic, while the remainder were attributed to competing mechanisms. Compared with non-cardioembolic events, cardioembolic aetiology was associated with younger median age (72 vs 81 years), lower proportions with good anticoagulant control (87/138 [63%] vs 34/41 [83%], p=0.017) and higher rates of peri-event missed or under-dosing (90/138 [65%] vs 18/41 [44%], p=0.014). In multivariable analysis, good control was independently associated with higher odds of a non-cardioembolic mechanism (adjusted odds ratio 3.67 [95% confidence interval 1.35-9.99], p=0.011). CONCLUSION: Most breakthrough IS/TIA events on oral anticoagulation were either associated with anticoagulant under-exposure (in patients with a cardioembolic aetiology) or a competing mechanism rather than anticoagulant failure. These findings highlight the importance of careful assessment to inform appropriate secondary prevention strategies.

Discussion

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Cite This Study

Mahawish et al. (2026) conducted a cross-sectional in Atrial fibrillation with breakthrough ischaemic stroke or TIA (n=179). Good anticoagulant control vs. Suboptimal anticoagulant control was evaluated on Non-cardioembolic mechanism of ischaemic stroke or TIA (aOR 3.67, 95% CI 1.35-9.99, p=0.011). Good anticoagulant control was independently associated with higher odds of a non-cardioembolic mechanism (aOR 3.67) in patients with atrial fibrillation experiencing a breakthrough ischemic stroke or TIA.

synapsesocial.com/papers/6a39557e4a780fc71663eb73 https://doi.org/10.26635/6965.7380

Topics

Atrial fibrillation

Anticoagulation in AF

Persistent AF management

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Mechanisms of ischaemic strokes and transient ischaemic attacks despite oral anticoagulation in patients with atrial fibrillation

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Mechanisms of ischaemic strokes and transient ischaemic attacks despite oral anticoagulation in patients with atrial fibrillation

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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