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November 01, 2016; 87 (18) Article

Early start of DOAC after ischemic stroke

Risk of intracranial hemorrhage and recurrent events

David J. Seiffge, Christopher Traenka, Alexandros Polymeris, Lisa Hert, Nils Peters, Philippe Lyrer, Stefan T. Engelter, Leo H. Bonati, Gian Marco De Marchis
First published September 30, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003283
David J. Seiffge
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Christopher Traenka
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Alexandros Polymeris
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Lisa Hert
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Nils Peters
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Philippe Lyrer
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Stefan T. Engelter
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Leo H. Bonati
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Gian Marco De Marchis
From the Department of Neurology and Stroke Center (D.J.S., C.T., A.P., L.H., N.P., P.L., S.T.E., L.H.B., G.M.D.M.), University Hospital of Basel; University of Basel (D.J.S.); and Neurorehabilitation Unit (S.T.E.), University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
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Citation
Early start of DOAC after ischemic stroke
Risk of intracranial hemorrhage and recurrent events
David J. Seiffge, Christopher Traenka, Alexandros Polymeris, Lisa Hert, Nils Peters, Philippe Lyrer, Stefan T. Engelter, Leo H. Bonati, Gian Marco De Marchis
Neurology Nov 2016, 87 (18) 1856-1862; DOI: 10.1212/WNL.0000000000003283

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Abstract

Objective: In patients with recent acute ischemic stroke (AIS) and atrial fibrillation, we assessed the starting time of direct, non–vitamin K antagonist oral anticoagulants (DOACs) for secondary prevention, the rate of intracranial hemorrhage (ICH), and recurrent ischemic events during follow-up.

Methods: We included consecutive patients with nonvalvular atrial fibrillation admitted to our hospital for AIS or TIA (index event) who received secondary prophylaxis with DOAC or vitamin K antagonists (VKAs). Follow-up was at least 3 months. In the primary analysis, we compared rates of ICH and recurrent ischemic events (AIS or TIA) between patients with early (≤7 days since event; DOACearly) and those with late (>7 days, DOAClate) start of DOAC.

Results: Two hundred four patients were included (median age 79 years, 89% AIS) and total follow-up time was 78.25 patient-years. One hundred fifty-five patients received DOAC with a median delay of 5 days after the index event (interquartile range 3–11) and 49 received VKA. DOAC was started early in 100 patients (65%). We observed one ICH (1.3%/y) and 6 recurrent AIS (7.7%/y). The ICH occurred in a patient taking VKA. No significant difference in the rate of recurrent AIS between DOACearly (5.1%/y) and DOAClate (9.3%/y, p = 0.53) was observed.

Conclusions: Even if DOACs are often started early after an index event, the risk of ICH appears to be low. Among all patients receiving anticoagulation, the rate of recurrent events was 6 times higher than the rate of ICH.

GLOSSARY

AF=
atrial fibrillation;
AIS=
acute ischemic stroke;
CHA2DS2-VASc=
congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category;
DOAC=
direct, non–vitamin K antagonist oral anticoagulant;
HAS-BLED=
hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly;
ICH=
intracranial hemorrhage;
INR=
international normalized ratio;
IQR=
interquartile range;
LMWH=
low-molecular-weight heparin;
mRS=
modified Rankin Scale;
NIHSS=
NIH Stroke Scale;
NOACISP=
Novel Oral Anticoagulants in Ischemic Stroke Patients;
OAC=
oral anticoagulation;
RCT=
randomized controlled trial;
VKA=
vitamin K antagonist

Footnotes

  • ↵* These authors contributed equally to this work as first authors.

  • ↵‡ These authors contributed equally to this work as senior authors.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 1852

  • Received March 30, 2016.
  • Accepted in final form June 27, 2016.
  • © 2016 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response to Prof. Kawada
    • David J Seiffge, Stroke Center and Neurology, University Hospital Basel, Switzerlanddavid.seiffge@usb.ch
    • Gian Marco De Marchis
    Submitted January 18, 2017
  • Direct oral anticoagulants in stroke patients with non-valvular atrial fibrillation
    • Tomoyuki Kawada, Professor, Nippon Medical Schoolkawada@nms.ac.jp
    Submitted January 09, 2017
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