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. 2021 Jan;89(1):42-53.
doi: 10.1002/ana.25917. Epub 2020 Oct 17.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Thomas R Meinel  1 , Mattia Branca  2 , Gian Marco De Marchis  3 , Krassen Nedeltchev  4 , Timo Kahles  4 , Leo Bonati  3 , Marcel Arnold  1 , Mirjam R Heldner  1 , Simon Jung  1 , Emmanuel Carrera  5 , Elisabeth Dirren  5 , Patrik Michel  6 , Davide Strambo  6 , Carlo W Cereda  7 , Giovanni Bianco  7 , Georg Kägi  8 , Jochen Vehoff  8 , Mira Katan  9 , Manuel Bolognese  10 , Roland Backhaus  11 , Stephan Salmen  12 , Sylvan Albert  13 , Friedrich Medlin  14 , Christian Berger  15 , Ludwig Schelosky  16 , Susanne Renaud  17 , Julien Niederhauser  18 , Christophe Bonvin  19 , Michael Schaerer  20 , Marie-Luise Mono  21 , Biljana Rodic  22 , Alexander A Tarnutzer  23 , Pasquale Mordasini  24 , Jan Gralla  24 , Johannes Kaesmacher  25 , Stefan Engelter  3   26 , Urs Fischer  1 , David J Seiffge  1 ; Investigators of the Swiss Stroke Registry
Affiliations

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Thomas R Meinel et al. Ann Neurol. 2021 Jan.

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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Conflict of interest statement

The following companies manufacture drugs involved in this study: Bayer (BY; rivaroxaban), Boehringer Ingelheim (BI; dabigatran), Pfizer/Bristol Meyer Squibb (PB; apixaban), and Daiichi Sankyo (DS; edoxaban). M.A.: personal fees, BY, DS, and PB. P.Mic.: research grants, the ERISTA program (PB). M.R.H.: personal fees, BY. L.B.: consultancy or advisory board fees or speaker's honoraria and travel grants, BY and PB. M.K.: research funding, DS. C.B.: nonfinancial support, BI, PB, and BY. M.Bol.: nonfinancial support, BY. C.C.: personal fees, BY, BI, and PB. D.S.: other, PB. G.M.D.M.: personal fees, BY and PB. K.N.: personal fees, BY and PB. All other authors: nothing to report.

Figures

FIGURE 1
FIGURE 1
Flow diagram of outcome completeness. AF = atrial fibrillation; IVT = intravenous thrombolysis; LVO = large vessel occlusion; mRS = modified Rankin Scale; MT = mechanical thrombectomy; NIHSS = National Institutes of Health Stroke Scale; sICH = symptomatic intracranial hemorrhage.
FIGURE 2
FIGURE 2
Frequency of prior anticoagulation treatment in patients with ischemic stroke. (A) Percentages of patients with atrial fibrillation among all ischemic stroke patients. (B) Percentages of patients with atrial fibrillation within the subgroup of ischemic stroke patients potentially eligible for intravenous thrombolysis. Note the decrease in VKA pretreatment with concomitant rapid increase in DOAC pretreatment in both patient groups. DOACs = direct oral anticoagulants; IVT = intravenous thrombolysis; VKA = vitamin K antagonist.
FIGURE 3
FIGURE 3
Functional outcome at 3 months according to prior anticoagulation treatment in patients with ischemic stroke. The dark gray line indicates a significant association of DOACs (aOR 1.24, 95% CI 1.01–1.51), but not VKA (light gray line, aOR 1.13, 95% CI 0.93–1.38) with good functional outcome (mRS 0–2). aOR = adjusted odds ratio; CI = confidence interval; DOACs = direct oral anticoagulants; mRS = modified Rankin Scale; VKA = vitamin K antagonist.
See this image and copyright information in PMC

Comment in

References

    1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta‐analysis of randomised trials. Lancet 2014;383:955–962. 10.1016/S0140-6736(13)62343-0. - DOI - PubMed
    1. Salazar CA, del Aguila D, Cordova EG. Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non‐valvular atrial fibrillation. Cochrane Database Syst Rev 2014;2014:CD009893 10.1002/14651858.CD009893.pub2. - DOI - PMC - PubMed
    1. Saxena R, Koudstaal PJ. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database Syst Rev 2004;18:CD000187 10.1002/14651858.cd000187.pub2. - DOI - PubMed
    1. Almutairi AR, Zhou L, Gellad WF, et al. Effectiveness and safety of non–vitamin K antagonist oral anticoagulants for atrial fibrillation and venous thromboembolism: a systematic review and meta‐analyses. Clin Ther 2017;39:1456–1478.e36. 10.1016/j.clinthera.2017.05.358. - DOI - PubMed
    1. Miyamoto S, Ikeda T, Ogawa S, et al. Clinical risk factors of thromboembolic and major bleeding events for patients with atrial fibrillation treated with rivaroxaban in Japan. J Stroke Cerebrovasc Dis 2020;29:1–9. 10.1016/j.jstrokecerebrovasdis.2019.104584. - DOI - PubMed