Thrombolysis May Be OK for DOAC-Treated Patients With Ischemic Stroke

Intravenous thrombolysis is associated with improved functional outcomes but no excess safety concerns in patients who have an acute ischemic stroke while taking a direct oral anticoagulant (DOAC), according to an analysis of the Get With The Guidelines-Stroke registry.

The odds of independent ambulation at discharge and likelihood of discharge to home were greater when this group received IV thrombolysis, researchers led by Shadi Yaghi, MD (Brown University, Providence, RI), report in a paper published online recently in the Journal of the American Heart Association.

Treatment was accompanied by a 3.5% rate of symptomatic intracranial hemorrhage (sICH), in line with the previously reported national average among patients who were not taking a DOAC at the time of IV thrombolysis.

Practice guidelines from the American Heart Association/American Stroke Association list use of a DOAC within the previous 48 hours as an exclusion criterion for IV thrombolysis in patients with acute ischemic stroke, mostly due to a lack of solid data on the safety of combining the treatments. Some clinicians, however, choose to use thrombolysis in DOAC-treated patients after weighing the potential risks and benefits.

Though this study suggests the practice is safe and effective, it needs to be confirmed with additional research, Yaghi indicated.

“This supports the need for randomized controlled trials testing the safety and efficacy of intravenous thrombolysis in patients who are on a DOAC. I think ultimately this is going to be needed to change the level of evidence and to change clinical practice,” he told TCTMD. He noted that additional data are on the way from the ongoing ACT-GLOBAL and DO-IT trials. There also is a US trial called ESTER-DOAC being planned.

The current analysis relied on data from the Get With The Guidelines-Stroke registry spanning from November 2014 to December 2022. It included patients who presented with acute ischemic stroke within 4.5 hours of when they were last known to have normal health status, had recent use of DOAC therapy (within the past 7 days), and were either given IV thrombolysis (n = 4,702) or excluded from thrombolysis solely because of DOAC-related coagulopathy (n = 44,205). Mean age overall was 75.1 years, and 50.5% of patients were men.

Those who received thrombolysis were younger on average, were more likely to have been brought to the hospital by emergency medical services, and had higher median NIHSS scores and rates of endovascular treatment.

Roughly half of patients were able to independently ambulate at discharge and be discharged home, with only slight differences between the thrombolysis and no-thrombolysis groups before adjustment for potential confounders. In fully adjusted logistic regression models, however, those who received IV thrombolysis had greater odds of ambulation at discharge (OR 1.35; 95% CI 1.21-1.50) and discharge to home (OR 1.33; 95% CI 1.22-1.46).

There was no excess risk of sICH compared with prior studies of non-DOAC-treated patients. The only factor associated with sICH was a higher NIHSS score (adjusted OR 1.05 per 1-point increase; 95% CI 95% CI 1.04-1.07).

The rate of systemic hemorrhage was 0.5%. Thrombolysis was associated with lower odds of a composite of in-hospital death or discharge to hospice (adjusted OR 0.70; 95% CI 0.62-0.80).

Yaghi said it’s not surprising that combining recent DOAC use and IV thrombolysis did not increase the rate of sICH, because “if someone had a stroke despite being on an anticoagulant, their levels are probably not high enough to pose a risk of bleeding with thrombolysis.” That is supported, he added, by data from prior studies.

The investigators acknowledge some limitations of the analysis, including the lack of information on the exact timing of the last DOAC ingestion and on the type of anticoagulant used, confounding bias related to the observational design, the lack of information on 90-day outcomes, and the large number of patients who were excluded because of missing data.