In patients who take non–vitamin K antagonist oral anticoagulants, alteplase is not associated with an increased risk of intracranial bleeds

Reference

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 2022;327(8):760-771.

Synopsis

Current guidelines recommend against the use of alteplase in patients who have taken non–vitamin K antagonist oral anticoagulants (NOACs) in the last 48 hours. Using data from a national US stroke registry during a 5-year period, these investigators identified 163,038 patients who had received intravenous alteplase for the treatment of acute ischemic stroke and had either taken no anticoagulants (n = 160,831) or taken NOACs within the prior 7 days (n = 2207). Patients in the NOAC group were older (median age 75 years vs 70 years in the no anticoagulant group), had more comorbidities, and had more severe strokes based on the National Institutes of Health Stroke Scale. Overall, 3% of patients in the entire cohort developed the primary outcome of symptomatic intracranial hemorrhage within 36 hours after receiving alteplase. After adjusting for factors such as patient demographics, stroke severity, and hospital-level variables, no significant difference was detected in the rate of the primary outcome between the 2 groups. Further, there were no differences in safety outcomes, including serious systemic bleeds, alteplase-related complications, or inpatient mortality. With regard to functional outcomes at discharge, patients in the NOAC group were more likely to be able to ambulate independently, be free of disabilities, be functionally independent, and be discharged to home. There were some key limitations in this study. First, for the patients who took NOACs, the precise timing of the last dose was unknown. The anticoagulant effect of NOACs may not be as potent beyond 48 hours of the last dose. Second, there may be a selection bias when deciding to give alteplase to patients who use NOACs. It is unclear from this study which patients would experience the most benefit and the least harm.