Thrombolysis Data in Stroke Patients on NOACs Encouraging

May 07, 2015

GLASGOW, Scotland — Patients taking one of the new oral anticoagulant drugs (NOACs) and who underwent recanalization therapy with thrombolysis, endovascular intervention, or both for an acute ischemic stroke did not have an excessive risk for intracerebral hemorrhage (ICH) in a new study.

The study, which used registries and patient records to examine the use of recanalization therapies in stroke patients taking anticoagulants, was presented at the recent inaugural European Stroke Organisation (ESO) Conference 2015 by David Seiffge, MD, University Hospital of Basel, Switzerland.

He explained that the current American Heart Association/American Stroke Association guidelines for the treatment of acute ischemic stroke state that: "The use of IV [intravenous] thrombolysis in patients taking direct thrombin inhibitors or direct factor Xa inhibitors may be harmful and is not recommended." The guidelines also state that "sensitive laboratory tests should be normal or the patient had not received any dose within the last 48 hours," he added.

Dr David Seiffge

Dr Seiffge noted that these recommendations were based on theoretical considerations and that clinical data are lacking, as all the pivotal trials of the NOACs for atrial fibrillation (ROCKET-AF, RELY, ARISTOTLE, ENGAGE-AF) excluded patients with acute stroke within the last 14 days.

He and his colleagues therefore conducted the current study to examine data on patients from 25 stroke centers who had undergone recanalization treatment while taking one of the new oral anticoagulant drugs (last intake <48 hours).

The study included 78 patients taking a NOAC, 441 patients taking vitamin K antagonist anticoagulants, and 8938 patients with no history of anticoagulant use. Baseline characteristics showed that patients receiving oral anticoagulants were older and had had more severe strokes than those not taking anticoagulants.

In the NOAC group, half the patients had taken their last dose within the previous 12 hours and 38% had taken their last dose 13 to 24 hours before reperfusion treatment.

The primary outcomes were safety endpoints: occurrence of any ICH, symptomatic ICH according to European-Australasian Acute Stroke Study II (ECASS-II) or National Institute of Neurologic Disorders and Stroke (NINDS) definitions, and death at 3 months.

These did not suggest a worse effect in patients receiving new oral anticoagulant compared with those not taking any anticoagulants.

Table 1. Safety Outcomes

Endpoint NOAC (%) Vitamin K Antagonist (%) No Anticoagulant (%)
Any ICH 18 26 17
Symptomatic ICH: ECASS II 2.6 6.5 5.0
Symptomatic ICH: NINDS 3.9 9.3 7.2
Death at 3 mo 23 27 14

 

Table 2. Secondary Endpoints: Neurologic Outcomes

Endpoint NOAC (%) Vitamin K Antagonist (%) No Anticoagulant (%)
NIHSS at 24 h 9 8 5
Major neurologic improvement 31.2 31.6 28.7
Favorable clinical outcome (mRS score, 0 - 2) at 3 mo 40.5 39.5 56.3

mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Scale.

 

None of these results were significantly different after propensity score matching.

An analysis focusing on higher and lower international normalized ratios (INRs) related to the vitamin K antagonist drugs suggested higher symptomatic ICH rates when defined by the ECASS II criteria in patients with an INR greater than 1.7 compared with those with an INR below 1.7.

In 24 patients taking rivaroxaban, the decision for thrombolysis or endovascular therapy was based on calibrated anti–factor Xa assays. Of these, 21 patients received thrombolysis; all of them had anti–factor Xa plasma levels under 100 ng/mL (mean, 21 ng/mL). Three patients with calibrated anti–factor Xa plasma level greater than 100 ng/mL received endovascular therapy without thrombolysis. None of these 24 patients had a symptomatic ICH.

Dr Seiffge told Medscape Medical News that his presentation included patients receiving IV thrombolysis only, intra-arterial treatment only, or a combination of both therapies. In all three cohorts — patients receiving NOACs, patients receiving vitamin K antagonists, and patients without prior anticoagulation — thrombolysis alone was used more often than intra-arterial therapy or both combined. A subgroup analysis for patients receiving thrombolysis only showed no different results than the main analysis, he added.

"Our take-home message is thrombolysis or intra-arterial therapy in selected patients with ischemic stroke undergoing treatment with new oral anticoagulants has a safety profile similar to when used in patients on subtherapeutic vitamin K antagonist treatment or in those without prior anticoagulation," he concluded.

He added, however, that further prospective studies are needed, including studies on the effect of specific coagulation tests. His team has therefore set up a prospective multicenter registry to study the NOACs in patients with ischemic and hemorrhagic stroke.

Parts of this study were funded by a grant from the Swiss Heart Foundation. Dr Seiffge has disclosed no other relevant financial relationships.

European Stroke Organisation (ESO) Conference 2015. Abstract 230. Presented April 18, 2015.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....