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

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

David J Seiffge  1   2   3 , Gian Marco De Marchis  2 , Masatoshi Koga  4 , Maurizio Paciaroni  5 , Duncan Wilson  1 , Manuel Cappellari  6 , Kosmas Macha Md  7 , Georgios Tsivgoulis  8   9 , Gareth Ambler  10 , Shoji Arihiro  4 , Leo H Bonati  2 , Bruno Bonetti  6 , Bernd Kallmünzer  7 , Keith W Muir  11 , Paolo Bovi  6 , Henrik Gensicke  2   12 , Manabu Inoue  4 , Stefan Schwab  7 , Shadi Yaghi  13 , Martin M Brown  1 , Philippe Lyrer  2 , Masahito Takagi  4 , Monica Acciarrese  5 , Hans Rolf Jager  14 , Alexandros A Polymeris  2 , Kazunori Toyoda  4 , Michele Venti  5 , Christopher Traenka  2 , Hiroshi Yamagami  4 , Andrea Alberti  5 , Sohei Yoshimura  4 , Valeria Caso  5 , Stefan T Engelter  2   12 , David J Werring  1 ; RAF, RAF-DOAC, CROMIS-2, SAMURAI, NOACISP, Erlangen, and Verona registry collaborators
Affiliations

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

David J Seiffge et al. Ann Neurol. .

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 (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). 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 OACprior (n = 1,195) and OACnaive (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%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (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.

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Conflict of interest statement

The following companies manufacture drugs involved in this study: Bayer (BY), Boehringer Ingelheim (BI), Pfizer/Bristol Meyer Squibb (PB), and Daiichi Sankyo (DSA). D.S.: scientific advisory boards, BY and PB. G.M.D.M.: travel honoraria, BY; speaker honoraria, PB. M.P.: honoraria for speaker bureau, BY, BI, PB, and DSA. K.Ma.: advisory boards, BI, BY, and DSA. S.T.E.: travel or speaker honoraria, BY, BI; scientific advisory boards, BY, BI, and PB; educational grant, PB. D.J.W.: speaking honoraria, BY. G.T.: speaking and advisory board honoraria, BI, DSA, and BY. All other authors have nothing to report.

Figures

Figure 1
Figure 1
Study flow chart. AF = atrial fibrillation; TIA = transient ischemic attack. [Color figure can be viewed at www.annalsofneurology.org]
Figure 2
Figure 2
Cumulative incidence function curves for the main outcome of recurrent acute ischemic stroke. (A) Primary analysis of patients taking oral anticoagulation prior to the index event (OACprior, dashed line) compared to those not taking anticoagulants prior to the index event (OACnaive, solid line). (B) Secondary analysis of patients that changed the type of anticoagulation (OACchanged, dashed line) compared to those who continued the same type of anticoagulation (OACunchanged, solid line). [Color figure can be viewed at www.annalsofneurology.org]
See this image and copyright information in PMC

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