Edoxaban in intracranial haemorrhage survivors with atrial fibrillation

Q: What did ENRICH-AF show at ESC Congress 2026?

Edoxaban did not reduce stroke or systemic embolism versus no anticoagulation (11.8% vs 12.8%; HR 0.88, 95% CI 0.61–1.26; p=0.48) and doubled major bleeding (11.6% vs 5.2%; HR 2.23).

Q: What are the key findings of this study?

Edoxaban did not significantly reduce stroke or systemic embolism versus no anticoagulation in AF patients with prior intracranial hemorrhage (11.8% vs 12.8%; HR 0.88; 95% CI 0.61-1.26; p=0.48).

Q: What is the clinical evidence from this study?

Study design: RCT. Population: high-risk atrial fibrillation and prior intracranial haemorrhage (n=948). Intervention: edoxaban vs. no anticoagulation. Primary outcome: stroke or systemic embolism (HR 0.88, 95% CI 0.61-1.26, p=0.48).

Zhan Wang

View all ESC 2026 trials

ENRICH-AFAtrial FibrillationOpen Access

Edoxaban in intracranial haemorrhage survivors with atrial fibrillation

View Full Paper

What happened

Edoxaban fails to reduce stroke or systemic embolism versus no anticoagulation in AF with prior ICH.

HR 0.88
95% CI 0.61-1.26
P=0.48
n=948
11.8% vs 12.8% at Mean 28 months

Does this change practice?

Where experts agree
Multiple clinicians converge on the same conclusion: edoxaban should not be used routinely in AF patients with prior intracranial hemorrhage, and anticoagulation decisions in this population must be individualized rather than applied broadly.
What this trial adds
Experts read ENRICH-AF as a clear null result that does not support routine anticoagulation with edoxaban in AF patients after intracranial hemorrhage, with the ischemic stroke benefit offset by excess bleeding, and they call for individualized decision-making while awaiting further trials.
Published field read
The reaction is overwhelmingly one-sided: no expert defends routine anticoagulation in this population after these results. The principal investigator and commentators alike stress that the bleeding harm outweighed any ischemic benefit, and that treatment decisions must be individualized. The live question is whether ongoing trials comparing different anticoagulants or using patient-level meta-analysis will identify subgroups that do benefit.

Still open

Questions raised in published commentary

Whether specific subgroups, such as patients with non-lobar hemorrhage, might still derive net benefit from anticoagulation remains unanswered.

Ongoing trials, including ASPIRE (apixaban vs. aspirin) and the COCROACH individual participant data meta-analysis, are needed to guide individualized therapy.

It is also uncertain whether left atrial appendage closure or other non-pharmacologic strategies should fill the gap for stroke prevention in these patients.

Context from published commentary. Source summaries are not a new guideline recommendation.

Who says what

Ashkan ShoamaneshPresenting authorMcMaster University

“Our findings do not support the use of edoxaban in unselected patients with AF after intracranial haemorrhage, but highlight the need for an individualised decision-making approach. Ongoing trials, including the double-blinded, randomised ASPIRE trial comparing apixaban vs. aspirin, will add to the evidence base. Additionally, a prospective, individual participant data meta-analysis of all trials (COCROACH) will ultimately provide useful additional insights on how best to individualise optimal stroke prevention in this very vulnerable patient population.”

Conference Coverage ↗

From published coverage, not an answer posted here.

Panteleimon Ε. PapakonstantinouResults readoutMater Private Hospital

Edoxaban nearly tripled hemorrhagic stroke, making individualization essential

X post ↗

Pishoy GoudaContextInterventional / Structural Cardiology · University of Alberta

ENRICH-AF failed to show a net benefit in the classic AF-after-ICH dilemma

X post ↗

Ahmed BennisResults readoutHeart Failure / Cardiomyopathy · Centre Hospitalier Universitaire Hassan II

No significant efficacy difference between edoxaban and control in this population

X post ↗

Show 6 more perspectives

Kevin Sheth

ContextNeurologist, Yale School of Medicine

Brain hemorrhage survivors must be enrolled in trials because they have been excluded from all prior anticoagulation studies

Original post ↗

C. Michael GibsonResults readoutInterventional / Structural Cardiology · Beth Israel Deaconess Medical Center

Edoxaban did not reduce stroke but increased major bleeding versus non-anticoagulant therapy

X post ↗

Martha Gulati

ContextCardiologist

Frames ENRICH-AF as addressing one of the hardest decisions in AF: whether to restart anticoagulation after intracranial hemorrhage.

X post ↗

Reza GhanavatiResults readoutPolytechnic University of Turin

Notes edoxaban did not reduce stroke or systemic embolism and increased major bleeding.

X post ↗

Michele Romoli@micheleromoli

“ENRICH-AF #ESCCongress 2026 In AF survivors of intracranial hemorrhage, edoxaban did not significantly reduce stroke/systemic embolism (11.8% vs 12.8%; HR 0.88). ↓ ischemic stroke: HR 0.57 ↑ hemorrhagic stroke: HR 2.99 ↑ major bleeding: HR 2.23 Infographic below”

X ↗

Shadi Yaghi@shadiyaghi2

“Congratulations @Ash_Shoamanesh and the ENRICH-AF team. Well done!”

X ↗

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Full evidence

Why the trial, key points, tables, limitations, PICO, abstract, media & sources

Why the trial?

Survivors of intracranial haemorrhage with atrial fibrillation face competing risks of ischaemic stroke and rebleeding, and were excluded from the pivotal anticoagulation trials. Whether restarting oral anticoagulation with edoxaban provides net benefit in this population was a long-standing evidence-free dilemma.

Does edoxaban reduce stroke or systemic embolism in patients with high-risk atrial fibrillation and prior intracranial haemorrhage?

Key Points

To evaluate the efficacy and safety of edoxaban compared to no anticoagulation in patients with high-risk atrial fibrillation and previous intracranial haemorrhage.
Investigator-initiated, open-label, blinded-endpoint randomized trial conducted across 174 sites in 20 countries.
Enrolled 948 participants (mean age 77 years; 39% women) randomized 1:1 to edoxaban (60 mg daily, label-adjusted to 30 mg) or no anticoagulation over a mean follow-up of 28 months.
Edoxaban did not significantly reduce the primary endpoint of stroke or systemic embolism compared with no anticoagulation (11.8% vs 12.8%; HR 0.88; 95% CI 0.61–1.26; p=0.48).
ISTH major bleeding occurred in 11.6% of patients assigned to edoxaban compared to 5.2% assigned to no anticoagulation (HR 2.23; 95% CI 1.39–3.59; p<0.001).

Evidence details

What drove the result?

Outcome	Edoxaban	No OAC
Stroke or systemic embolism	11.8%	12.8%
HR 0.88 (95% CI 0.61-1.26); p=0.48 - fewer ischaemic strokes and MIs offset by ~3-fold more haemorrhagic strokes (counts not reported)

Limitations & tradeoffs

Safety

ISTH major bleeding 11.6% vs 5.2%; HR 2.23 (95% CI 1.39-3.59); p<0.001.

Design limitations

open-label design (endpoints blinded), and enrollment of lobar intraparenchymal and convexity subarachnoid haemorrhage stopped after a 2023 DSMB review, so the final population is selected.

Statistical certainty

per-arm event counts are unavailable; results derive from the congress press release without a simultaneous publication.

Structured PICO

Does edoxaban reduce stroke or systemic embolism in patients with high-risk atrial fibrillation and prior intracranial haemorrhage?

Population

948 older adults (mean age 77, 39% women) with high-risk atrial fibrillation and prior intracranial haemorrhage, followed for a mean of 28 months.

Intervention

Edoxaban 60 mg daily (label-adjusted to 30 mg)

Comparator

No anticoagulation

Outcome

Stroke or systemic embolismcomposite

Main Result

Hazard Ratio: 0.88 (95% CI 0.61–1.26)

Absolute Event Rate: 11.8% vs 12.8%

p-value: p=0.48

In patients with atrial fibrillation and prior intracranial hemorrhage, edoxaban did not reduce stroke or systemic embolism compared to no anticoagulation, but significantly increased major bleeding.

Limitations

No simultaneous results paper was available at presentation; source is the ESC Congress 2026 press release.

Discussion

No takes yet. Share an insight, caveat, or question.

Expert reaction

What experts said about ENRICH-AF

ESC Congress 2026

Atrial fibrillation evidence still forming

What 4 experts said about this trial's result

1supportive1neutral1cautious1critical

“Our findings do not support the use of edoxaban in unselected patients with AF after intracranial haemorrhage, but highlight the need for an individualised decision-making approach. Ongoing trials, including the double-blinded, randomised ASPIRE trial comparing apixaban vs.…”
Ashkan Shoamanesh, Stroke neurologist, McMaster University · Source ·

Expert labels are toward ENRICH-AF's result, from named public quotes (n=4). As of Aug 30, 2026.

Where experts stand

Experts read ENRICH-AF as a clear null result that does not support routine anticoagulation with edoxaban in AF patients after intracranial hemorrhage, with the ischemic stroke benefit offset by excess bleeding, and they call for individualized decision-making while awaiting further trials.

The reaction is overwhelmingly one-sided: no expert defends routine anticoagulation in this population after these results. The principal investigator and commentators alike stress that the bleeding harm outweighed any ischemic benefit, and that treatment decisions must be individualized. The live question is whether ongoing trials comparing different anticoagulants or using patient-level meta-analysis will identify subgroups that do benefit.

Agreement

Multiple clinicians converge on the same conclusion: edoxaban should not be used routinely in AF patients with prior intracranial hemorrhage, and anticoagulation decisions in this population must be individualized rather than applied broadly.

3 clinicians say this directly

What they’re arguing about

supportiveneutralcautiouscritical

Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.

Still unclear

Whether specific subgroups, such as patients with non-lobar hemorrhage, might still derive net benefit from anticoagulation remains unanswered. Ongoing trials, including ASPIRE (apixaban vs. aspirin) and the COCROACH individual participant data meta-analysis, are needed to guide individualized therapy. It is also uncertain whether left atrial appendage closure or other non-pharmacologic strategies should fill the gap for stroke prevention in these patients.

Key expert perspectives

ASAshkan ShoamaneshStroke neurologist, McMaster UniversityPractice takeAug 30

Do not anticoagulate unselected AF patients after intracranial hemorrhage, but individualize and await more data

Shoamanesh, the trial's principal investigator, states that the findings do not support edoxaban in unselected patients with AF after intracranial hemorrhage. He highlights the need for individualized decision-making and points to the ongoing ASPIRE trial and the COCROACH individual participant data meta-analysis as sources of future guidance. He urges physicians to wait for more data before acting on anticoagulation in high-risk subgroups.

Distilled from 4 of their postsOriginal post Original post Original post Original post

Panteleimon Ε. PapakonstantinouMater Private HospitalResults readoutAug 30

Edoxaban nearly tripled hemorrhagic stroke, making individualization essential

Papakonstantinou emphasizes that edoxaban more than doubled major bleeding and nearly tripled hemorrhagic stroke, reinforcing that individualisation of anticoagulation is the key takeaway from ENRICH-AF.

Distilled from their postX post

Pishoy GoudaInterventional / Structural Cardiology · University of AlbertaContextAug 29

ENRICH-AF failed to show a net benefit in the classic AF-after-ICH dilemma

Gouda framed the trial around the fundamental clinical tension: without anticoagulation stroke risk rises, but with it the concern for recurrent intracranial hemorrhage persists. He notes the primary endpoint was not met.

Distilled from 2 of their postsX post X post

Implication

Avoid edoxaban in AF patients with prior intracranial hemorrhage due to net harm; challenges assumptions favoring anticoagulation from indirect evidence.

Abstract

ENRICH-AF was an investigator-initiated, open-label, blinded-endpoint, event-driven trial at 174 sites in 20 countries. Patients with high-risk atrial fibrillation and prior intracranial haemorrhage were randomised 1:1 to edoxaban 60 mg daily (label-adjusted to 30 mg) or no anticoagulation. After a 2023 DSMB review, no further patients with lobar intraparenchymal or convexity subarachnoid haemorrhage were enrolled. The 948 participants had a mean age of 77 years; 39% were women. Over a mean 28 months of follow-up, edoxaban did not significantly reduce the primary endpoint of stroke or systemic embolism versus no anticoagulation (11.8% vs 12.8%; HR 0.88; 95% CI 0.61–1.26; p=0.48). Ischaemic stroke and myocardial infarction fell, but this was offset by an almost three-fold excess in haemorrhagic stroke. ISTH major bleeding occurred in 11.6% with edoxaban and 5.2% with no anticoagulation (HR 2.23; 95% CI 1.39–3.59; p<0.001). Findings do not support edoxaban in unselected AF patients after intracranial haemorrhage. No simultaneous results paper was available at presentation; source is the ESC Congress 2026 press release.

Coverage & sources

Journal, society, and media accounts. Useful signal, not independent expert judgment.

Cite This Study

Zhan Wang (2026) conducted an RCT in high-risk atrial fibrillation and prior intracranial haemorrhage (n=948). edoxaban vs. no anticoagulation was evaluated on stroke or systemic embolism (HR 0.88, 95% CI 0.61-1.26, p=0.48). Edoxaban did not significantly reduce stroke or systemic embolism versus no anticoagulation in AF patients with prior intracranial hemorrhage (11.8% vs 12.8%; HR 0.88; 95% CI 0.61-1.26; p=0.48).

synapsesocial.com/papers/6a8fbb6217152b56e6b64817 https://www.escardio.org/news/press/press-releases/safer-stroke-prevention-strategies-are-needed-for-patients-with-atrial-fibrillation-after-intracranial-haemorrhage/

Does this change practice?

Where experts agree
Multiple clinicians converge on the same conclusion: edoxaban should not be used routinely in AF patients with prior intracranial hemorrhage, and anticoagulation decisions in this population must be individualized rather than applied broadly.
What this trial adds
Experts read ENRICH-AF as a clear null result that does not support routine anticoagulation with edoxaban in AF patients after intracranial hemorrhage, with the ischemic stroke benefit offset by excess bleeding, and they call for individualized decision-making while awaiting further trials.
Published field read
The reaction is overwhelmingly one-sided: no expert defends routine anticoagulation in this population after these results. The principal investigator and commentators alike stress that the bleeding harm outweighed any ischemic benefit, and that treatment decisions must be individualized. The live question is whether ongoing trials comparing different anticoagulants or using patient-level meta-analysis will identify subgroups that do benefit.