Breakthrough Stroke on Anticoagulation: Identifiable Causes Double Recurrence Risk

This large real-world cohort quantifies how often modifiable factors, including drug interactions, cancer, and non-cardioembolic mechanisms, underlie ischemic stroke despite adherent oral anticoagulation and links them to worse 90-day outcomes.

📅 Journal publication: Aug 17, 2026 · Last updated: Oct 5, 2026

direct oral anticoagulantsvitamin K antagonistsatrial fibrillationbreakthrough ischemic strokedrug interactionsproton pump inhibitorsactive cancersecondary preventionmyocardial infarctionobservational cohortASPERA-R Anticoagulation / Hematology

Also in Neurology / Neuropharmacology

Background Information

Ischemic strokes occur even with anticoagulation; drug interactions may be key.

Despite oral anticoagulation, ischemic strokes can still occur in patients with atrial fibrillation and understanding the causes is critical for reducing these events. In 43.9% of patients experiencing breakthrough ischemic strokes, potential causes were identified, notably interacting drugs in 28.4%. These causes were associated with a higher risk of stroke recurrence (HR 2.04). Identifying and managing potential causes such as drug interactions and competing etiologies can significantly influence patient outcomes by reducing stroke recurrence risk. Interacting drugs and other causes of breakthrough strokes demand focused management to prevent recurrence.

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Authors: De Santis F, Foschi M, Gabriele F, D'Anna L, Zini A, Paolucci M, Forlivesi S, Migliaccio L, Viola MM, Rizzo AC, Sessa M, Schwarz G, Tortorella R, Banerjee S, Desai G, Ahmed KF, Prandin G, Pantoni L, Mele F, Scopelliti G, Cova I, Valente M, Maisano D, Antonelli L, Bagnato MR, Di Mauro G, Bernocchi F, Di Donna MG, Casolla B, Diallo SM, Alvarez B, Contenti J, González-Martìn L, Rigual R, Fuentes B, Hervás-Testal C, Candelaresi P, Andreone V, De Mase A, Spina E, de Sousa DA, Souza MA, Fior A, Serôdio M, Caliandro P, Zauli A, Reale G, Abdelalim A, Ahmed S, Ismail SA, Zhang L, Latimer T, Elboghdady M, Elbassiouny A, Roushdy T, Shokri H, Ferrari F, Loizzo ND, Mazzacane F, Guarino M, Barone V, Forti P, Rinaldi G, Rossi MV, Laterza V, Frisullo G, Rizzo PA, Broccolini A, Mannino M, Terruso V, Caggiula M, Rizzo A, Fonseca AC, Antunes B, Barbosa AM, Budincevic H, Crnac P, Viticchi G, Silvestrini M, Barba L, Musienko V, Otto M, Lochner P, Landau B, Buddha S, Khalil R, Piscaglia MG, Minguzzi E, Zedde M, Nasreldein A, Vinciguerra L, Costa LR, Elsayed AE, AlBanna M, Tudisco L, Mosconi MG, Polymeris AA, Merlino G, Sacco S, Ornello R

Citation: De Santis F, Foschi M, Gabriele F, et al. Decoding the causes of ischemic stroke despite ongoing oral anticoagulation and their clinical impact: the ASPERA-R study. Journal of neurology. 2026;273(9). doi:10.1007/s00415-026-14039-x

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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