Prior Use of Oral Anticoagulants and Bleeding Risk With Alteplase in Patients With Stroke

nurse assessing stroke victim
nurse assessing stroke victim
Researchers sought to evaluate the safety and functional outcomes of intravenous alteplase among patients who took NOACs prior to stroke and compare the outcomes of patients who did not take long-term anticoagulants.

Patients who were receiving non-vitamin K antagonist oral anticoagulants (NOACs) within 7 days of receiving intravenous alteplase for acute ischemic stroke (AIS) were not at increased risk for intracranial hemorrhage, according to study findings published in JAMA.

NOACs have become the first-line therapy to prevent ischemic stroke among patients with nonvalvular atrial fibrillation. Although highly efficacious, 1%-2% of patients receiving NOACs have an ischemic stroke yearly. As NOAC usage has become widely adopted, the number of patients exposed to NOACs presenting with AIS has increased.

In order to better assess whether NOAC usage increases risk for intracranial hemorrhage, data were sourced from two interrelated registries (GWTG-Stroke and ARAMIS). Patients (N=163,038) with AIS who received intravenous alteplase within 4.5 hours of symptom onset between 2015 and 2020 at 1752 hospitals in the United States were assessed for clinical outcomes on the basis of whether they had been taking NOACs within 7 days of AIS.

Patients were aged median 70 (interquartile range [IQR], 59-61) years, 49.1% were women, and 1.4% were taking NOACs. The cohort of patients using NOACs were older, had more comorbidities, and had more severe strokes.

A total of 3.2% of all patients developed symptomatic intracranial hemorrhage within 36 hours of receiving alteplase. Stratified by NOAC use, the rate of intracranial hemorrhage was 3.7% among users and 3.2% among non-users.

After adjusting for baseline features, NOAC exposure was not associated with increased risk for intracranial hemorrhage (adjusted odds ratio [aOR], 0.88; 95% CI, 0.70-1.10).

Numerically more of the NOAC cohort had inpatient mortality (6.3% vs 4.9%) and inpatient mortality or discharge to hospice (12.4% vs 9.4%). After adjusting for baseline features, however, neither inpatient mortality (aOR, 0.84; 95% CI, 0.69-1.01) nor inpatient mortality or discharge to hospice (aOR, 0.87; 95% CI, 0.76-1.00) were associated with NOAC exposure.

NOAC use was associated with functional independence at hospital discharge (aOR, 1.27; 95% CI, 1.11-1.45), ability to ambulate independently at hospital discharge (aOR, 1.25; 95% CI, 1.12-1.40), free from disability at discharge (aOR, 1.22; 95% CI, 1.06-1.42), and discharge to home (aOR, 1.17; 95% CI, 1.06-1.29).

This study may have been limited by the baseline differences between NOAC users and nonusers.

“Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Kam W, Holmes DN, Hernandez AF, et al. Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase. JAMA. Published online February 10, 2022. doi:10.1001/jama.2022.0948