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. 2025 May;27(2):217-227.
doi: 10.5853/jos.2024.04322. Epub 2025 May 31.

Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis

Alexandros A Polymeris  1   2 , Masatoshi Koga  3 , Daniel Strbian  4 , Adhiyaman Vedamurthy  5 , Manju Krishnan  6 , Mattia Branca  7 , Thomas Horvath  8 , Martina Goeldlin  8 , Gek Shim  9 , Christoph Gumbinger  10 , Liqun Zhang  11 , Espen Saxhaug Kristoffersen  12   13 , Philippe Desfontaines  14 , Peter Vanacker  15 , Angelika Alonso  16 , Sven Poli  17   18 , Ana Paiva Nunes  19 , Nicoletta G Caracciolo  20 , Markus Kneihsl  21   22 , Timo Kahles  23 , Daria Giudici  24 , Silja Räty  4 , Marjaana Tiainen  4 , Jesse Dawson  25 , Urs Fischer  8 ; ELAN Investigators
Affiliations

Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis

Alexandros A Polymeris et al. J Stroke. 2025 May.

Abstract

Background and purpose: Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.

Methods: A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.

Results: Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66-1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65-1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30-1.08], HRweighted 0.57 [0.30-1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56-6.63], HRweighted 1.88 [0.56-6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.

Conclusion: Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.

Keywords: Anticoagulants; Antiplatelet bridging; Antiplatelets; Atrial fibrillation; Ischemic stroke; Timing.

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Conflict of interest statement

Conflicts of interest

AAP: Research support from the Swiss Academy of Medical Sciences (SAMS)/Bangerter-Foundation, Swiss Heart Foundation (SHF), Swiss National Science Foundation (SNSF), Freiwillige Akademische Gesellschaft Basel; MaKo: honoraria from AstraZeneca, Bayer-Yakuhin, Daiichi-Sankyo, Mitsubishi Tanabe Pharma Corporation, BMS/Pfizer, BMS/Janssen, Otsuka Pharmaceutical; research support from Daiichi-Sankyo and Nippon- Boehringer-Ingelheim (all outside this work). MB is affiliated with CTU Bern, Department of Clinical Research, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and forprofit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. For an up-to-date list of CTU Bern’s conflicts of interest, see https://dcr.unibe.ch/services/declaration_of_interest/index_eng. html; MG: Grants from SAMS/Bangerter-Foundation (for the submitted work), Swiss Stroke Society, European Stroke Organisation, Mittelbauvereinigung der Universität Bern and Inselgruppe AG. Congress grants from European Academy of Neurology (EAN) and Pfizer (outside this work); SP: Research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi-Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen; speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi- Sankyo, Portola, and Werfen (all outside this work); MaKn: Grant from EAN (unrelated to this work); advisory board Novartis and BMS Pfizer; MT: Speaker fees Angelini Pharma (outside this work); JD: Speaker fees Pfizer, BMS, Boehringer-Ingelheim, Daiichi- Sankyo, Medtronic, Bayer. Research funding from Pfizer, BMS, and the Stroke Association; UF: research support from SNSF and SHF; PI of the ELAN trial, Co-PI of the DISTAL, TECNO, SWIFT DIRECT and SWITCH trials; research grants from Medtronic (BEYOND SWIFT, SWIFT DIRECT), Stryker, Rapid medical, Penumbra, and Phenox (DISTAL); consultancies for Medtronic, Stryker, and CSL Behring (fees paid to institution); participation on an advisory board for Alexion/Portola, Boehringer-Ingelheim, Biogen and Acthera (fees paid to institution); member of a clinical event committee of the COATING study (Phenox) and member of the data and safety monitoring committee of the TITAN, LATE_MT, and IN EXTREMIS trials; president of the Swiss Neurological Society.

The remaining authors declare no relevant conflicts of interest.

Figures

Figure 1.
Figure 1.
Unadjusted and inverse probability of treatment weighted (A) OR and (B) HR estimates for the effect of use versus non-use of antiplatelets before DOAC initiation on the composite outcome and all its individual components. Weighting for baseline variables included age, sex, stroke size classification (minor, moderate, major), NIHSS score, ELAN trial randomization group (early or late treatment), CHA2DS2-VASc score, myocardial infarction, and all other cardiovascular comorbidities presented in Table 1. Major bleeding includes ICH and major extracranial bleeding. Logistic models included 1,975 participants (excluding those who died from non-vascular causes, withdrew consent, or were lost to follow-up), while survival analysis included all 2,013 participants. OR, odds ratio; HR, hazard ratio; CI, confidence interval; DOAC, direct oral anticoagulant; NIHSS, National Institutes of Health Stroke Scale; ELAN, Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation; CHA2DS2-VASc, congestive heart failure, hypertension, age >75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex; ICH, intracranial hemorrhage.
Figure 2.
Figure 2.
Cumulative incidence curves for the (A) composite and (B-E) individual outcomes at 30 days according to antiplatelet use (blue) versus non-use (red) using the Aalen-Johansen estimator to account for competing risks. Major bleeding includes intracranial hemorrhage and major extracranial bleeding. DOAC, direct oral anticoagulant.
Figure 3.
Figure 3.
Net clinical benefit of antiplatelet use over non-use in weighted events possibly prevented per 100 person-months (solid line) with 95% confidence intervals (grey shaded area). ICH, intracranial hemorrhage.
See this image and copyright information in PMC

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