Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

David J Seiffge; Gian Marco De Marchis; Masatoshi Koga; Maurizio Paciaroni; Duncan Wilson; Manuel Cappellari; Kosmas Macha Md; Georgios Tsivgoulis; Gareth Ambler; Shoji Arihiro; Leo H Bonati; Bruno Bonetti; Bernd Kallmünzer; Keith W Muir; Paolo Bovi; Henrik Gensicke; Manabu Inoue; Stefan Schwab; Shadi Yaghi; Martin M Brown; Philippe Lyrer; Masahito Takagi; Monica Acciarrese; Hans Rolf Jager; Alexandros A Polymeris; Kazunori Toyoda; Michele Venti; Christopher Traenka; Hiroshi Yamagami; Andrea Alberti; Sohei Yoshimura; Valeria Caso; Stefan T Engelter; David J Werring; RAF, RAF-DOAC, CROMIS-2, SAMURAI, NOACISP, Erlangen, and Verona registry collaborators

doi:10.1002/ana.25700

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

Ann Neurol. 2020 Feb 12;87(5):677-687. doi: 10.1002/ana.25700. Online ahead of print.

Authors

David J Seiffge^{1

2

3}, Gian Marco De Marchis², Masatoshi Koga⁴, Maurizio Paciaroni⁵, Duncan Wilson¹, Manuel Cappellari⁶, Kosmas Macha Md⁷, Georgios Tsivgoulis^{8

9}, Gareth Ambler¹⁰, Shoji Arihiro⁴, Leo H Bonati², Bruno Bonetti⁶, Bernd Kallmünzer⁷, Keith W Muir¹¹, Paolo Bovi⁶, Henrik Gensicke^{2

12}, Manabu Inoue⁴, Stefan Schwab⁷, Shadi Yaghi¹³, Martin M Brown¹, Philippe Lyrer², Masahito Takagi⁴, Monica Acciarrese⁵, Hans Rolf Jager¹⁴, Alexandros A Polymeris², Kazunori Toyoda⁴, Michele Venti⁵, Christopher Traenka², Hiroshi Yamagami⁴, Andrea Alberti⁵, Sohei Yoshimura⁴, Valeria Caso⁵, Stefan T Engelter^{2

12}, David J Werring¹; RAF, RAF-DOAC, CROMIS-2, SAMURAI, NOACISP, Erlangen, and Verona registry collaborators

Affiliations

¹ Stroke Research Center, Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
² Neurology and Stroke Center, Department of Clinical Research, University Hospital of Basel, University of Basel, Basel, Switzerland.
³ Department of Neurology and Stroke Center, University Hospital of Bern, Bern, Switzerland.
⁴ Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
⁵ Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
⁶ Stroke Unit, Department of Neuroscience, University Hospital Integrated Trust of Verona, Verona, Italy.
⁷ Department of Neurology, University of Erlangen-Nürnberg, Erlangen, Germany.
⁸ Second Department of Neurology, National and Kapodistrian University of Athens School of Medicine, Attikon University Hospital, Athens, Greece.
⁹ Department of Neurology, University of Tennessee Health Science Center, Memphis, TN.
¹⁰ Department of Statistical Science, University College London, London, United Kingdom.
¹¹ Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
¹² Neurorehabilitation Unit, University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Basel, Switzerland.
¹³ NYU Langone Health, New York, NY.
¹⁴ Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, London, United Kingdom.

Abstract

Objective: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.

Methods: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC_prior ) with those without prior oral anticoagulation (OAC_naive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC_changed ) with those who continued the same anticoagulation as secondary prevention (OAC_unchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA₂ DS₂ -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC_prior (n = 1,195) and OAC_naive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC_prior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC_changed (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC_unchanged (n = 585).

Interpretation: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA₂ DS₂ -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.

Abstract

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