Vascular disease

Thrombolysis a challenge for stroke patients taking DOACS

Thursday, 6 Feb 2020


Patients who have a stroke or TIA while on a DOAC are missing out on timely thrombolysis compared to patients on warfarin, Australian research suggests.  

A Victorian study of 154 patients with a new diagnosis of stroke while prescribed an oral anticoagulant found 45% of those on warfarin received tPA within 4.5 hours. However only 16% of patients receiving one of the DOACs received reperfusion.

The retrospective study found clinical, radiological and functional outcomes of stroke were similar in the warfarin treated group compared to the DOAC treated group. 

The majority of patients in the cohort had presented with mild symptoms (77%) and most (69%) were able to be discharged directly to home.

The study found 55% of the patients on warfarin had subtherapeutic INR on presentation. DOAC plasma levels were not tested in any of the patients on dabigatran, rivaroxaban or apixaban.

However self-reported medication non-adherence was more common in patients on a DOAC (13%) than those on warfarin (2%).

The findings raises questions about the lack of testing in patients on DOACs particularly when  “plasma DOAC levels may aid decision making in the acute setting when thrombolysis is indicated.”

“In acute ischaemic stroke, the benefit of thrombolysis is highly time-dependent but there are many barriers in obtaining the result quickly. Infrequent testing means reagents are not readily thawed and ready to go, standards need to be run each time and the laboratory must be well resourced to have trained scientists available,” the study authors said. 

The authors added that at the time of the study, the average time to return an INR was about 30 minutes or less compared to 60-90 minutes for an urgent DOAC level.

“Current experience of intravenous thrombolysis in DOAC patients is mostly limited to using antidote on spec or instigating treatment without DOAC specific testing in the majority of patients,” they wrote in the Internal Medicine Journal.

Senior author on the paper Dr Philip Choi, a neurologist at Eastern Health and Monash University, told the limbic that stroke while on DOACs would become more common given an ageing population, the increasing prevalence of indications such as atrial fibrillation, and the move to DOAC use over warfarin. 

“And I guess this paper highlights that although it [a DOAC] is a very easy to use medication without routine therapeutic drug level testing, when you do have a situation such as ischaemic stroke in patients, it is a more difficult management problem compared to if they were on warfarin.”

Dr Choi said the main barrier was a general lack of research in the area to date – both locally and internationally. 

“The association between DOAC drug level and level of anticoagulation in a patient is not as direct as INR and warfarin. The range of so-called therapeutic DOAC levels doesn’t exist and I guess that is the difficulty.” 

He added that Australia was the only country so far with definitive recommendations around DOAC drug level testing including cut-off levels below which thrombolysis can be safely considered.

Dr Choi said Box Hill Hospital had been funded for a study to systematically test DOAC levels in all patients presenting with ischaemic stroke while on a DOAC. 

“And I think that would really address the limitations in this paper – that we don’t really know whether patients are taking the medication or not, and if they are taking it, what are the levels.”

He said the study would also assess the utility of point-of-care testing using a urine dipstick analysis that could give clinicians a quick DOAC positive/negative finding within 10 minutes.

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