Early Versus Delayed Anticoagulation in Acute Ischemic Stroke According to Atrial Fibrillation Subtype and Time of Diagnosis: Subgroup Analysis of the OPTIMAS Randomized Controlled Trial
BACKGROUND: After acute ischemic stroke, it is uncertain whether the time of atrial fibrillation (AF) diagnosis (before or after stroke) or AF subtype (paroxysmal or permanent) modifies the treatment effect of early versus delayed direct oral anticoagulant (DOAC) initiation. METHODS: OPTIMAS was a randomized, parallel-group, open-label trial with blinded outcome assessment. Participants with acute ischemic stroke and AF were randomized 1:1 to early (within 4 days) or delayed (day 7-14) DOAC initiation. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, and systemic arterial embolism. In this trial subgroup analysis, the prespecified subgroup of interest was time of AF diagnosis, classified as before or after the qualifying stroke. We also investigated AF subtype classified as persistent or paroxysmal. We fitted mixed effects logistic regression models with interaction terms between each subgroup and treatment allocation. We also investigated associations between AF time of diagnosis or subtype and outcomes using multivariable logistic regression. RESULTS: =0.377. AF time of diagnosis was not associated with outcome events. Compared with paroxysmal AF, persistent AF was independently associated with an increased risk of the primary outcome (adjusted odds ratio, 2.10 [95% CI, 1.19-3.68]). CONCLUSIONS: We found no evidence that AF time of diagnosis or subtype modify the effects of early DOAC treatment. Persistent AF was independently associated with approximately double the risk of the primary outcome compared with paroxysmal AF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.
Authors
- Amalia Ndoutoumou (ORCID: https://orcid.org/0000-0002-0982-1222)
- Robert Fenner (ORCID: https://orcid.org/0000-0002-5819-9601)
- Aneet Gill (ORCID: https://orcid.org/0009-0005-9248-8406)
- Emilia Caverly (ORCID: https://orcid.org/0000-0002-4420-713X)
- CH Sim
- Caroline J Doré
- Maryam Balogun (ORCID: https://orcid.org/0009-0006-8006-0522)
- J.D Serrano Reyes
- Liz Aram
- Kate Bennett (ORCID: https://orcid.org/0000-0002-2358-4497)
- Ekaterina Bordea (ORCID: https://orcid.org/0000-0002-3772-7049)
- Mike James
- Rachael Hunter (ORCID: https://orcid.org/0000-0002-7447-8934)
- Norin Ahmed (ORCID: https://orcid.org/0000-0001-8798-5217)
- Hannah Cohen (ORCID: https://orcid.org/0000-0003-2032-390X)
- D. Werring
- Tishok Vanniyasingam
- Marisa Chau (ORCID: https://orcid.org/0000-0003-2965-1870)
- Nicholas Freemantle
- Hannah Sims
- Mairead Cullen
- Sue Massingham
- Iwona Mazurczak
- Jenny Philip
- Philip S Nash
- James Lyon
- DG Esteban
- S Hunte
- M Evans
- A. Smith
- V Dave
- F Robinson
- S Sakthivel
- Gary A. Ford
- V Cvoro
- J Howe
- G Thomas
- Y Abousleiman
- Macey L. Murray
- P Ferdinand
- L Dixon
- R Parakramawansha
- L Mallon
- H Bains
- LH Griebel
- I Ponce
- R Price
- A Asaipillai
- C Kamara
- L Reid
- M Bhandari
- E O’Brien
- Bo G. Norrving
- R Varquez
- J Benjamin
- S Hewson
- P Slade
- M Couser
- A Naqvi
- TL Margaret
- L Sekaran
- L Broad
- M White
- S Al-Hussayni
- J Gardner
- B Clarke
- J Angus
- J Joseph
- W Murad
- L Poolon
- J Mitchell-Douglas
- T Patel
- L Knibbs
- M Castanheira
- F Justin
- C Fornolles
- L. M. Zhang
- Gregory Y.H. Lip
- Jonathan G. Best
- E Richards
- S Saxena
- J Kho
- T Anjum
- T Hughes
- K Harkness
- S Storton
- B Jelley
- S Sundayi
- Stefan Engelter
- K Thavanesan
- L Binnie
- R Teal
- S Francis
- Hakim-Moulay Dehbi
- Nikola Sprigg
- H Hughes
- S Mashate
- M Krishnan
Institutions
- University College London Hospitals NHS Foundation Trust (GB)
- Medical University of Białystok (PL)
- University of Liverpool (GB)
- Queen Mary University of London (GB)
- University of Exeter (GB)
- Royal Devon and Exeter Hospital (GB)
- University of Oxford (GB)
- Liverpool Heart and Chest Hospital (GB)
- MRC Clinical Trials Unit at UCL (GB)
- Institute of Mental Health (GB)
- Felix Platter-Hospital (CH)
- Skåne University Hospital (SE)
- Oxford University Hospitals NHS Trust (GB)
- University College London (GB)
- Aalborg University (DK)
Publication Details
- Journal
- Stroke
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1161/strokeaha.125.055037
- Primary Topic
- Atrial Fibrillation Management and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 0.00