Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

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Abstract

Objective

The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes.

Methods

This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months.

Results

Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2–11]) compared with VKA (6, [2–14]) and controls (7, [3–15], p < 0.001; quantile regression: β −2.1, 95% confidence interval [CI] −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51).

Interpretation

Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53

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Most cited references 39

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Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

William J. Powers, Alejandro A Rabinstein, Teri Ackerson … (2019)

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

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Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

Christian Ruff, Robert Giugliano, Eugene Braunwald … (2014)

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.

Elaine Hylek, Alan S Go, Yuchiao Chang … (2003)

The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR. We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files. Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0. Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation. Copyright 2003 Massachusetts Medical Society

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Author and article information

Contributors

David J. Seiffge:

ORCID: https://orcid.org/0000-0003-3890-3849

david.seiffge@insel.ch

Journal

Journal ID (nlm-ta): Ann Neurol

Journal ID (iso-abbrev): Ann Neurol

Journal ID (doi): 10.1002/(ISSN)1531-8249

Journal ID (publisher-id): ANA

Title: Annals of Neurology

Publisher: John Wiley & Sons, Inc. (Hoboken, USA )

ISSN (Print): 0364-5134

ISSN (Electronic): 1531-8249

Publication date (Electronic): 17 October 2020

Publication date (Print): January 2021

Volume: 89

Issue: 1 ( doiID: 10.1002/ana.v89.1 )

Pages: 42-53

Affiliations

[ ¹ ] Department of Neurology Inselspital, Bern University Hospital, and University of Bern Bern Switzerland

[ ² ] Clinicial Trials Unit Bern University of Bern Bern Switzerland

[ ³ ] Department of Neurology and Stroke Center University Hospital Basel and University of Basel Basel Switzerland

[ ⁴ ] Department of Neurology Kantonsspital Aarau Aarau Switzerland

[ ⁵ ] Department of Neurology Hôpitaux Universitaires de Genève Geneva Switzerland

[ ⁶ ] Stroke Center, Neurology Service, Lausanne University Hospital Lausanne Switzerland

[ ⁷ ] Stroke Center, Neurocenter of Southern Switzerland Lugano Switzerland

[ ⁸ ] Department of Neurology Kantonsspital St. Gallen St. Gallen Switzerland

[ ⁹ ] Department of Neurology University Hospital Zurich Basel Switzerland

[ ¹⁰ ] Neurocenter, Cantonal Hospital of Lucerne Lucerne Switzerland

[ ¹¹ ] Hirslanden Hospital Zurich Glattpark Switzerland

[ ¹² ] Spitalzentrum Biel Biel Switzerland

[ ¹³ ] Cantonal Hospital Graubuenden Chur Switzerland

[ ¹⁴ ] Stroke Unit, Cantonal Hospital Fribourg Fribourg Switzerland

[ ¹⁵ ] Spital Sarganserland Grabs Grabs Switzerland

[ ¹⁶ ] Neurology Cantonal Hospital Münsterlingen Münsterlingen Switzerland

[ ¹⁷ ] Neurology Cantonal Hospital Neuchatel Neuchâtel Switzerland

[ ¹⁸ ] Stroke Unit Groupement hospitalier de l'ouest lémanique Nyon Switzerland

[ ¹⁹ ] Hôpital du Valais Sion Switzerland

[ ²⁰ ] Bürgerspital Solothurn Solothurn Switzerland

[ ²¹ ] Stadtspital Waid und Triemli Zurich Switzerland

[ ²² ] Cantonal Hospital Winterthur Winterthur Switzerland

[ ²³ ] Cantonal hospital of Baden Baden Switzerland

[ ²⁴ ] Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, and University of Bern Bern Switzerland

[ ²⁵ ] Department of Neurology Institute of Diagnostic and Interventional Neuroradiology, Institute of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, and University of Bern Bern Switzerland

[ ²⁶ ] Neurology and Neurorehabilitation, University Department of Geriatic Medicine Felix Platter University of Basel Basel Switzerland

Author notes

[*] [* ] Address correspondence to Dr Seiffge, Department of Neurology, Inselspital, Freiburgstrasse 8, CH‐3010, Switzerland, E‐mail: david.seiffge@ 123456insel.ch

Equally contributing senior authors.

Author information

Thomas R. Meinel https://orcid.org/0000-0002-0647-9273

Mattia Branca https://orcid.org/0000-0002-8063-7882

Gian Marco De Marchis https://orcid.org/0000-0002-0342-9780

Mirjam R. Heldner https://orcid.org/0000-0002-3594-2159

Emmanuel Carrera https://orcid.org/0000-0003-0045-5382

Carlo W. Cereda https://orcid.org/0000-0002-6479-1476

David J. Seiffge https://orcid.org/0000-0003-3890-3849

Article

Publisher ID: ANA25917

DOI: 10.1002/ana.25917

PMC ID: 7756294

PubMed ID: 32996627

SO-VID: 90ebd9c2-2b4b-4a09-b991-24c1ca11c248

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 03 June 2020

Date revision received : 23 September 2020

Date accepted : 23 September 2020

Page count

Figures: 3, Tables: 3, Pages: 12, Words: 8274

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cover-date January 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:23.12.2020

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

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Abstract

Objective

Methods

Results

Interpretation

Related collections

Stroke MRI

Most cited references 39

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.

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