Thrombolysis Safe in Stroke Patients on Oral Anticoagulants

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months compared to patients who received IVT but who did not receive DOAC.

Dr Jan Purrucker

"At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis," said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

"The main question we have to answer is, is IVT safe in acute ischemic stroke patients pretreated with direct oral anticoagulants or not?"

The findings were presented May 6 at the European Stroke Organisation Conference (ESOC) 2022 in Lyon, France.

A "Daily Clinical Problem"

As many as 20% of patients with AF experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

As reported by Medscape Medical News, a recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

"In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke," Purrucker said. "They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem."

Purrucker and colleagues in New Zealand and Switzerland launched an international observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared to the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio [aOR], 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% CI, 0.99 – 1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

"The question is whether we are so confident in these data that we would change our clinical practice now," Purrucker said.

Infrastructure Needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings for Medscape Medical News.

"The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal," Chun said. "The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke."

Most hospitals lack the equipment necessary to test DOAC levels and don't have immediate access to DOAC reversal agents, Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

"Infrastructure needs to be in place to ensure timely delivery of IVT to these patients," Chun added. "This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents."

Chun added, "Large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT."

But such a study may not be feasible, Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Purrucker said he hopes a change in guidelines might be taken up in the future.

"But it should be good academic practice, to first let the results be externally evaluated, eg, during the manuscript submission process," he said. "But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations."

The study received no commercial funding. Purrucker and Chun reported no relevant financial relationships.

European Stroke Organisation Conference (ESOC) 2022: Abstract 1236. Presented May 6, 2022.

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