Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists

Elias Auer; Sebastién Frey; Johannes Kaesmacher; Arsany Hakim; David J Seiffge; Martina Goeldlin; Marcel Arnold; Urs Fischer; Simon Jung; Thomas Raphael Meinel

doi:10.1007/s00415-019-09412-y

Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists

J Neurol. 2019 Sep;266(9):2263-2272. doi: 10.1007/s00415-019-09412-y. Epub 2019 Jun 4.

Authors

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland.
² Department of Neurology, Institute of Diagnostic and Interventional Neuroradiology, Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland.
³ Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland. thomas.meinel@insel.ch.

PMID: 31165232
DOI: 10.1007/s00415-019-09412-y

Abstract

Background: Although direct oral anticoagulants (DOAC) have proven at least equally effective in the prevention of acute ischemic stroke (AIS) in patients with atrial fibrillation as compared to the vitamin K antagonists (VKA), no reliable data on the severity of AIS of DOAC patients as compared to VKA is available.

Methods: Using a prospectively collected cohort of AIS patients, we performed univariate and multivariate (displayed as adjusted Odds Ratios, OR and 95% confidence intervals, 95% CI) analyses regarding the severity of AIS in patients with preceding DOAC (N = 210) versus VKA (N = 173) therapy. Additionally, we provide a sensitivity analysis considering only patients with warranted therapeutic anticoagulation activity.

Findings: In a comprehensive stroke center population, the frequency of AIS under DOAC was multiple times higher than previously reported at around 6% of all AIS and steadily increasing. National Institute of Health Stroke Scale (NIHSS) in VKA patients (median 7, IQR 2-14) was equal to DOAC (median 5, IQR 2-16) on univariate analysis (P = 0.229). According to the multivariable linear logistic regression analysis adjusting for confounders of severe stroke, VKA was not significantly associated with higher NIHSS scores (β - 0.165, 95% CI - 1.874 to 1.545, P = 0.850) as compared to DOAC. Also in the sensitivity analysis considering only patients with warranted therapeutic OAC therapy, VKA was not significantly associated with higher NIHSS scores (β - 1.392, 95% CI - 3.506 to 0.721, P = 0.195) as compared to DOAC. However, VKA as compared to DOAC was significantly associated with lower rates of good functional outcome at three months (0.527, 95% CI 0.300-0.928), but not with increased mortality (aOR 1.825, 95% CI 0.780-4.273).

Interpretation: Ischemic stroke in patients taking DOAC is an important and frequent scenario. Stroke severity in our real world population dataset is equal in patients taking VKA and DOAC, also in the case of warranted anticoagulation therapy. Preceding VKA as compared to DOAC was associated with lower rates of good functional outcome without excess mortality, but a causal relationship cannot be proven by our study design.

Keywords: Acute ischemic stroke; Anticoagulation; Atrial fibrillation; DOAC; NIHSS; Severity.

Publication types

Comparative Study
Observational Study

MeSH terms

Administration, Oral
Aged
Aged, 80 and over
Anticoagulants / administration & dosage*
Cohort Studies
Female
Humans
Male
Pre-Exposure Prophylaxis / trends
Prospective Studies
Registries
Severity of Illness Index*
Stroke / diagnosis*
Stroke / drug therapy*
Vitamin K / antagonists & inhibitors*

Substances

Anticoagulants
Vitamin K