Argatroban Associated with Neuroprotection After Acute Ischemic Stroke

Results from a randomized clinical trial published in JAMA Neurology revealed that adding argatroban to standard antiplatet therapy was associated with significantly improved neurological function in those with acute ischemic stroke and signs of early neurological deterioration (END). END often occurs within the first 48 hours after acute ischemic stroke and is associated with poor outcome. Even with antiplatelet therapy, most people with END experience worsening of their condition. Argatroban is a direct thrombin inhibitor, with preclinical evidence suggesting that the agent potentially may be neuroprotective.

The EASE clinical trial (NCT04275180) was a prospective, multicenter, open-label, blinded-endpoint, randomized study conducted in 28 medical sites throughout China.

1. The final analysis included 628 adults aged ≥18 years with acute ischemic stroke and END identified by an increase of ≥2 points on the total National Institutes of Health Stroke Scale (NIHSS).

2. Participants were randomized to 1 of 2 treatment groups within 48 hours of symptom onset:

• Standard therapy ([n=303] including mono or dual antiplatelet therapy)
• Standard therapy along with intravenous argatroban for 7 days as a continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days (n=298)

3. A score of 0 to 3 on the modified Rankin Scale (mRS) at 90 days was evaluated as a primary endpoint for good functional outcome.

At 90 days, 80.5% of participants in the argatroban + standard therapy group and 73.3% of participants in the standard therapy group achieved the primary endpoint (risk difference, 7.2%; 95% CI, 0.6% to 14.0%; risk ratio, 1.10; 95% CI, 1.01 to 1.20; P=.04). This finding demonstrates that the addition of argatroban to standard antiplatelet therapy was associated with a significantly greater likelihood that patients with an acute ischemic stroke and END would experience good functional outcomes. Analysis of adverse event occurrence showed no additional risk of major intracranial or extracranial hemorrhage associated with argatroban use.