Anticoagulants in Acute Ischemic Stroke Patients Treated With Intravenous Alteplase

20s male patient in hospital bed listening to doctor and nurse in hospital
Investigators evaluated the safety and functional outcomes of IV alteplase in patients who have had an acute ischemic stroke and are taking NOACs.

Among patients treated with non–vitamin K antagonist oral anticoagulants (NOACs) within 7 days preceding an acute ischemic stroke treated with intravenous alteplase, there was no significant association of increased risk of intracranial hemorrhage compared with patients with no use of anticoagulants. These findings were published in the Journal of the American Medical Association.

Alteplase is the drug of choice to treat acute ischemic stroke and seems to still be the only FDA-approved drug for this use. Patients with acute ischemic stroke are currently advised against the use of intravenous alteplase if they are already taking NOACs. A study was conducted to compare the safety and functional outcomes of intravenous alteplase in patients with acute ischemic stroke who were being treated with NOACs prior to stroke with patients not taking long-term anticoagulants.

The study was a retrospective cohort study that included 163,038 patients (median age 70 years [IQR, 59-81]; 49.1% women) with acute ischemic stroke, treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals between April 2015 and March 2020. Patients were participating in the Get With the Guideline (GWTG)-Stroke program and the study also included complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry.

The primary outcome was symptomatic intracranial hemorrhage within 36 hours after intravenous alteplase treatment. Of these patients, 2207 (median age 75 years; [IQR, 64-82]) were taking NOACs and 160,831 (median age 70 years [IQR, 58-81]) were not taking anticoagulants prior to their stroke. Patients taking NOACs also had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5-17] vs 7 [IQR, 4-14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9%-4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1%-3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70-1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]).

Limitations reported in this study included that it was an observational cohort analysis instead of a randomized clinical trial, there was a strong potential for selection bias related to which patients taking NOACs received alteplase, and a substantial proportion of patients taking NOACs within the GWTG-Stroke cohort may have had an interruption in the NOAC intake for more than 48 hours. There were also some patients that may have received reduced dosing of alteplase, and the dosing information was not captured in the registry. Levels of drug-specific coagulation assays were also not available and the results may not be generalizable to patients treated at non-registry hospitals.

“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 wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ 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 22, 2022. doi:10.1001/jama.2022.0948