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 2025. 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 - Administration, Oral
KW - Aged
KW - Aged, 80 and over
KW - Anticoagulants/administration & dosage
KW - Atrial Fibrillation/drug therapy
KW - Denmark/epidemiology
KW - Drug Administration Schedule
KW - Female
KW - Hemorrhage/chemically induced
KW - Humans
KW - Male
KW - Recurrence
KW - Registries
KW - Risk Assessment
KW - Risk Factors
KW - Stroke/prevention & control
KW - Time Factors
UR - http://www.scopus.com/inward/record.url?scp=105011212003&partnerID=8YFLogxK
U2 - 10.1136/heartjnl-2024-325343
DO - 10.1136/heartjnl-2024-325343
M3 - Journal article
C2 - 40670148
SN - 1355-6037
VL - 112
JO - Heart
JF - Heart
IS - 5
ER -