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Holding tPA for All DOAC Users Not the Way to Go, Stroke Docs Say

<ѻý class="mpt-content-deck">— Clinical conundrum could be solved by a point-of-care DOAC test
MedpageToday
A computer rendering of a stroke

Current guidance on how to manage stroke patients on direct oral anticoagulant (DOAC) therapy isn't right, but there aren't the validated tools needed to do better either, lamented clinicians.

DOACs taken for stroke prevention may turn out to be the very reason for withholding treatment in acute stroke: from the American Heart Association and American Stroke Association have a class III recommendation against thrombolysis within 48 hours of last DOAC intake for fear of bleeding.

"We strongly disagree with this generalized recommendation," wrote a group led by David Seiffge, MD, of the University Hospital of Bern, Switzerland, in published online in JAMA Neurology.

"Available data show that carefully selected patients taking prior DOAC therapy have similar bleeding risks to patients not taking DOAC after IV thrombolysis," they argued.

Rather than categorically excluding DOAC users from recanalization therapies, stroke treatment could incorporate selection of patients for thrombolysis based on drug-specific assays (e.g., thromboelastography) and use of reversal agents before thrombolysis (e.g., idarucizumab [Praxbind] reversal of dabigatran [Pradaxa], andexanet alfa [Andexxa] reversal of factor Xa inhibitors) if necessary, Seiffge and colleagues suggested.

Thromboelastography shows promise for point-of-care testing, as it measures viscoelastic properties of clotting blood and correlates with serum DOAC levels. However, selection for thrombolysis using this method has yet to be reported, and it needs to be more broadly available in the first place.

"Why are anti-Xa activity assays not more available? A strong call for further validation and more availability of these tests should be a priority, rather than a recommendation to fly by the seat of our pants, so to speak, by giving a reversal agent and hoping for the best," wrote Alexandra Czap, MD, of the University of Texas Health Science Center, and James Grotta, MD, of Memorial Hermann Hospital-Texas Medical Center, both in Houston, in piece.

The strategy of anticoagulant reversal before IV thrombolysis also suffers from the lack of data beyond observational reports.

Reversal agents are not all equal, either, as andexanet alfa as compared with idarucizumab provides "much less reliable and durable reversal at a much higher cost for the most commonly used DOACs," according to Czap and Grotta.

"[H]aving a point-of-care test available in the prehospital setting or emergency department would make all the difference in being sure that the patient needs the reversal agent and it has been successful in reversing DOAC activity," the pair wrote.

Both published viewpoints alluded to the low likelihood of convincing randomized data coming out to assess DOAC reversal strategies before stroke thrombolysis.

Seiffge's group raised another clinical conundrum: whether to offer bridging thrombolysis before endovascular thrombectomy among DOAC users in acute ischemic stroke.

This decision "should depend on several clinical factors including rapid access to an endovascular center and the type of DOAC the patient is taking," the group said.

"In summary, the decision of how to treat a patient having an acute ischemic stroke while taking a DOAC is among the most complex and nuanced in acute stroke management. Uncertainty regarding time between the last DOAC dose and symptom onset and DOAC activity factor into risk of bleeding, risk of clotting, and chance of benefit from the use of a reversal agent prior to a thrombolytic agent," according to Czap and Grotta.

"A point-of-care test would go a long way to help clinicians with these areas of uncertainty, and development of such a test should be a priority. In the meantime, cases need to be carefully individualized and optimally managed by stroke specialists," the duo concluded.

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    Nicole Lou is a reporter for ѻý, where she covers cardiology news and other developments in medicine.

Disclosures

Seiffge reported serving on the advisory board for Bayer and Pfizer; receiving personal fees from Portola; and getting grants from the Swiss National Science Foundation, Bangerter-Rhyner-Foundation, Swiss Society of Neurology, and Bayer Foundation.

Grotta receives consulting fees from Haemonetics and grants from CSL Behring.

Czap had no disclosures.

Primary Source

JAMA Neurology

Seiffge DJ, et al "Administering thrombolysis for acute ischemic stroke in patients taking direct oral anticoagulants: to treat or how to treat" JAMA Neurol 2021; DOI: 10.1001/jamaneurol.2021.0287.

Secondary Source

JAMA Neurology

Czap AL, Grotta JC "Complexities of reperfusion therapy in patients with ischemic stroke pretreated with direct oral anticoagulants: to treat or not, and how?" JAMA Neurol 2021; DOI: 10.1001/jamaneurol.2021.0290.