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Decoding the causes of ischemic stroke despite ongoing oral anticoagulation and their clinical impact: the ASPERA-R

Federico De Santis1, Matteo Foschi1,2, Francesca Gabriele1

  • 1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy.

Journal of Neurology
|August 16, 2026
PubMed
Abstract

Insights

Breakthrough strokes in atrial fibrillation patients on anticoagulants often have identifiable causes like drug interactions. Recognizing these factors is key to reducing recurrent stroke risk.

Area of Science:

  • Cardiology
  • Neurology
  • Pharmacology

Background:

  • Oral anticoagulants (OACs) are crucial for stroke prevention in atrial fibrillation (AF).
  • Despite OAC therapy, 1-2% of AF patients experience breakthrough ischemic strokes annually.
  • Mechanisms behind these strokes, especially drug interactions, require further investigation.

Purpose of the Study:

  • Identify potential causes of breakthrough ischemic strokes in AF patients on OACs.
  • Assess the impact of these causes on patient outcomes, focusing on drug interactions.
  • Evaluate the association between interacting drugs and adverse cardiovascular events.

Main Methods:

  • ASPERA-R: A multicenter retrospective study of AF patients with ischemic stroke despite OAC therapy.
  • Included patients on direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).
  • Analyzed potential causes: interacting drugs, cancer, competing etiologies; assessed 90-day outcomes using Cox regression and IPW.

Main Results:

  • Nearly half (43.9%) of 1649 patients had at least one potential cause for stroke.
  • Interacting drugs (28.4%) and competing etiologies (24.3%) were most common.
  • Potential causes correlated with a 2-fold increased risk of recurrent ischemic stroke (HR 2.04).

Conclusions:

  • Identifiable causes contribute to approximately half of breakthrough strokes in AF patients.
  • These factors are linked to a higher risk of recurrent ischemic stroke.
  • Individualized management strategies focusing on drug interactions and other causes are needed to reduce recurrence.
Keywords:
Atrial fibrillationBreakthrough ischemic strokeCancerOral anticoagulantsPolypharmacy

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