Recurrent Ischemic Stroke Despite Dabigatran Therapy: Unexpectedly Low Anti-IIa Activity Revealing Pharmacokinetic Treatment Failure

Direct oral anticoagulants (DOACs) are the preferred therapy for stroke prevention in atrial fibrillation, but rare cases of pharmacokinetic resistance have been described, and objective biological confirmation remains scarce in the literature. We report the case of a man who experienced three ischemic strokes between the ages of 57 and 60 over a four-year period. The first episode, of cryptogenic origin, was attributed to a patent foramen ovale (PFO) associated with an interatrial septal aneurysm, leading to percutaneous closure. The recurrence led to a diagnosis of paroxysmal atrial fibrillation via an implantable cardiac monitor. Despite treatment with dabigatran 150 mg twice daily, a third stroke occurred. Pharmacokinetic treatment failure was documented by anti-IIa chromogenic testing, which had dropped to a residual level below 15 ng/mL despite supervised administration, adequate renal function, and no identified drug interactions. Switching to apixaban resulted in satisfactory on-therapy levels from Day 3. This case illustrates the value of prolonged rhythm monitoring after PFO closure and demonstrates apparent pharmacokinetic treatment failure with dabigatran, objectively confirmed by anti-IIa activity testing. Pharmacokinetically guided DOAC switching should be considered when recurrent ischemic events occur despite apparently adequate anticoagulation.