Timing of anticoagulation restart after serious bleeding in atrial fibrillation

Nour Al-Hussainy; Kristian Kragholm; Søren Lundbye-Christensen; Christian Torp-Pedersen; Manan Pareek; Susette Krohn Therkelsen; Gregory Y.H. Lip; Sam Riahi

doi:10.1136/heartjnl-2024-325343

Timing of anticoagulation restart after serious bleeding in atrial fibrillation

Nour Al-Hussainy^*
, Kristian Kragholm
, Søren Lundbye-Christensen
, Christian Torp-Pedersen
, Manan Pareek
, Susette Krohn Therkelsen
, Gregory Y.H. Lip
, Sam Riahi

^*Corresponding author for this work

Medicine 1

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Restarting direct oral anticoagulants (DOACs) after a serious bleeding event in patients with atrial fibrillation (AF) presents a clinical dilemma, with limited evidence on the balance between stroke prevention and recurrent bleeding risk.

METHODS: Using nationwide Danish registries (2012-2021), we identified AF patients (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex category (female) (CHA₂DS₂-VASc score ≥2)) who experienced a first serious bleeding event while on DOAC therapy. Patients were grouped by timing of DOAC restart: within 60 days ('early restarters') vs after 60 days ('late restarters'). HRs for stroke, recurrent bleeding and a composite endpoint (stroke or serious bleeding) were estimated using multivariable Cox models. A secondary analysis examined outcomes across six time-varying antithrombotic treatment regimens.

RESULTS: Among 10 291 patients who survived 60 days postbleeding, 5970 restarted DOAC early and 4321 later. The early restart group had a lower rate of stroke (HR 0.89; 95% CI 0.74 to 1.08), but the interval includes both moderate benefit and no clear difference, indicating uncertainty in the stroke reduction. Recurrent bleeding was more frequent in early restarters (HR 1.21; 95% CI 1.07 to 1.36). In the time-varying analysis, DOAC monotherapy was associated with reduced stroke risk compared with no treatment (HR 0.78; 95% CI 0.68 to 0.89). However, bleeding risk was also higher during DOAC monotherapy (HR 1.26; 95% CI 1.15 to 1.38).

CONCLUSIONS: Restarting DOACs early after a serious bleeding event in AF patients may reduce stroke risk but is associated with an increased risk of recurrent bleeding. DOAC monotherapy appears to offer the best stroke protection, though with elevated bleeding risk. These findings highlight the need for individualised decision-making and further trials to define optimal timing for DOAC resumption.

Original language	English
Pages (from-to)	253-260
Number of pages	8
Journal	Heart
Volume	112
Issue number	5
Early online date	16 Jul 2025
DOIs	https://doi.org/10.1136/heartjnl-2024-325343
Publication status	Published - 12 Feb 2026

Keywords

Atrial Fibrillation
Stroke
Recurrence
Risk Assessment
Drug Administration Schedule
Administration, Oral
Humans
Risk Factors
Male
Hemorrhage/chemically induced
Anticoagulants/administration & dosage
Denmark/epidemiology
Time Factors
Stroke/prevention & control
Aged, 80 and over
Atrial Fibrillation/drug therapy
Female
Registries
Aged

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10.1136/heartjnl-2024-325343

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@article{239ddc1f6edd4472bd787830bc194a2b,

title = "Timing of anticoagulation restart after serious bleeding in atrial fibrillation",

abstract = "BACKGROUND: Restarting direct oral anticoagulants (DOACs) after a serious bleeding event in patients with atrial fibrillation (AF) presents a clinical dilemma, with limited evidence on the balance between stroke prevention and recurrent bleeding risk.METHODS: Using nationwide Danish registries (2012-2021), we identified AF patients (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex category (female) (CHA₂DS₂-VASc score ≥2)) who experienced a first serious bleeding event while on DOAC therapy. Patients were grouped by timing of DOAC restart: within 60 days ('early restarters') vs after 60 days ('late restarters'). HRs for stroke, recurrent bleeding and a composite endpoint (stroke or serious bleeding) were estimated using multivariable Cox models. A secondary analysis examined outcomes across six time-varying antithrombotic treatment regimens.RESULTS: Among 10 291 patients who survived 60 days postbleeding, 5970 restarted DOAC early and 4321 later. The early restart group had a lower rate of stroke (HR 0.89; 95\% CI 0.74 to 1.08), but the interval includes both moderate benefit and no clear difference, indicating uncertainty in the stroke reduction. Recurrent bleeding was more frequent in early restarters (HR 1.21; 95\% CI 1.07 to 1.36). In the time-varying analysis, DOAC monotherapy was associated with reduced stroke risk compared with no treatment (HR 0.78; 95\% CI 0.68 to 0.89). However, bleeding risk was also higher during DOAC monotherapy (HR 1.26; 95\% CI 1.15 to 1.38).CONCLUSIONS: Restarting DOACs early after a serious bleeding event in AF patients may reduce stroke risk but is associated with an increased risk of recurrent bleeding. DOAC monotherapy appears to offer the best stroke protection, though with elevated bleeding risk. These findings highlight the need for individualised decision-making and further trials to define optimal timing for DOAC resumption.",

keywords = "Atrial Fibrillation, Stroke, Recurrence, Risk Assessment, Drug Administration Schedule, Administration, Oral, Humans, Risk Factors, Male, Hemorrhage/chemically induced, Anticoagulants/administration \& dosage, Denmark/epidemiology, Time Factors, Stroke/prevention \& control, Aged, 80 and over, Atrial Fibrillation/drug therapy, Female, Registries, Aged",

author = "Nour Al-Hussainy and Kristian Kragholm and S{\o}ren Lundbye-Christensen and Christian Torp-Pedersen and Manan Pareek and \{Krohn Therkelsen\}, Susette and Lip, \{Gregory Y.H.\} and Sam Riahi",

note = "{\textcopyright} World Health Organization 2026. Licensee BMJ.",

year = "2026",

month = feb,

day = "12",

doi = "10.1136/heartjnl-2024-325343",

language = "English",

volume = "112",

pages = "253--260",

journal = "Heart",

issn = "1355-6037",

publisher = "BMJ Publishing Group",

number = "5",

}

TY - JOUR

T1 - Timing of anticoagulation restart after serious bleeding in atrial fibrillation

AU - Al-Hussainy, Nour

AU - Kragholm, Kristian

AU - Lundbye-Christensen, Søren

AU - Torp-Pedersen, Christian

AU - Pareek, Manan

AU - Krohn Therkelsen, Susette

AU - Lip, Gregory Y.H.

AU - Riahi, Sam

N1 - © World Health Organization 2026. Licensee BMJ.

PY - 2026/2/12

Y1 - 2026/2/12

N2 - BACKGROUND: Restarting direct oral anticoagulants (DOACs) after a serious bleeding event in patients with atrial fibrillation (AF) presents a clinical dilemma, with limited evidence on the balance between stroke prevention and recurrent bleeding risk.METHODS: Using nationwide Danish registries (2012-2021), we identified AF patients (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex category (female) (CHA₂DS₂-VASc score ≥2)) who experienced a first serious bleeding event while on DOAC therapy. Patients were grouped by timing of DOAC restart: within 60 days ('early restarters') vs after 60 days ('late restarters'). HRs for stroke, recurrent bleeding and a composite endpoint (stroke or serious bleeding) were estimated using multivariable Cox models. A secondary analysis examined outcomes across six time-varying antithrombotic treatment regimens.RESULTS: Among 10 291 patients who survived 60 days postbleeding, 5970 restarted DOAC early and 4321 later. The early restart group had a lower rate of stroke (HR 0.89; 95% CI 0.74 to 1.08), but the interval includes both moderate benefit and no clear difference, indicating uncertainty in the stroke reduction. Recurrent bleeding was more frequent in early restarters (HR 1.21; 95% CI 1.07 to 1.36). In the time-varying analysis, DOAC monotherapy was associated with reduced stroke risk compared with no treatment (HR 0.78; 95% CI 0.68 to 0.89). However, bleeding risk was also higher during DOAC monotherapy (HR 1.26; 95% CI 1.15 to 1.38).CONCLUSIONS: Restarting DOACs early after a serious bleeding event in AF patients may reduce stroke risk but is associated with an increased risk of recurrent bleeding. DOAC monotherapy appears to offer the best stroke protection, though with elevated bleeding risk. These findings highlight the need for individualised decision-making and further trials to define optimal timing for DOAC resumption.

AB - BACKGROUND: Restarting direct oral anticoagulants (DOACs) after a serious bleeding event in patients with atrial fibrillation (AF) presents a clinical dilemma, with limited evidence on the balance between stroke prevention and recurrent bleeding risk.METHODS: Using nationwide Danish registries (2012-2021), we identified AF patients (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex category (female) (CHA₂DS₂-VASc score ≥2)) who experienced a first serious bleeding event while on DOAC therapy. Patients were grouped by timing of DOAC restart: within 60 days ('early restarters') vs after 60 days ('late restarters'). HRs for stroke, recurrent bleeding and a composite endpoint (stroke or serious bleeding) were estimated using multivariable Cox models. A secondary analysis examined outcomes across six time-varying antithrombotic treatment regimens.RESULTS: Among 10 291 patients who survived 60 days postbleeding, 5970 restarted DOAC early and 4321 later. The early restart group had a lower rate of stroke (HR 0.89; 95% CI 0.74 to 1.08), but the interval includes both moderate benefit and no clear difference, indicating uncertainty in the stroke reduction. Recurrent bleeding was more frequent in early restarters (HR 1.21; 95% CI 1.07 to 1.36). In the time-varying analysis, DOAC monotherapy was associated with reduced stroke risk compared with no treatment (HR 0.78; 95% CI 0.68 to 0.89). However, bleeding risk was also higher during DOAC monotherapy (HR 1.26; 95% CI 1.15 to 1.38).CONCLUSIONS: Restarting DOACs early after a serious bleeding event in AF patients may reduce stroke risk but is associated with an increased risk of recurrent bleeding. DOAC monotherapy appears to offer the best stroke protection, though with elevated bleeding risk. These findings highlight the need for individualised decision-making and further trials to define optimal timing for DOAC resumption.

KW - Atrial Fibrillation

KW - Stroke

KW - Recurrence

KW - Risk Assessment

KW - Drug Administration Schedule

KW - Administration, Oral

KW - Humans

KW - Risk Factors

KW - Male

KW - Hemorrhage/chemically induced

KW - Anticoagulants/administration & dosage

KW - Denmark/epidemiology

KW - Time Factors

KW - Stroke/prevention & control

KW - Aged, 80 and over

KW - Atrial Fibrillation/drug therapy

KW - Female

KW - Registries

KW - Aged

U2 - 10.1136/heartjnl-2024-325343

DO - 10.1136/heartjnl-2024-325343

M3 - Article

C2 - 40670148

SN - 1355-6037

VL - 112

SP - 253

EP - 260

JO - Heart

JF - Heart

IS - 5

ER -

Timing of anticoagulation restart after serious bleeding in atrial fibrillation

Abstract

Keywords

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