Jay Shah, MD
Kate M, Gioia L, Buck B, Sivakumar L, Jeerakathil T, Shuaib A, and Butcher K. Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation. Stroke. 2015
Balancing risk of ischemic stroke and hemorrhage risk is a particular challenge in vascular neurology. It has been well established that patients with transient ischemic attack (TIA) are at greater risk for recurrent stroke, particularly within days and weeks following TIA. Strategies to ameliorate this risk depend on the stroke mechanism. For example, dual anti-platelet therapy would be adequate for intracranial atherosclerosis but insufficient for atrial fibrillation (AF) where anticoagulation is required. However, safety of dabigatran, a direct oral anticoagulant, prescribed within 2 weeks of minor stroke is unknown as previous safety trials excluded such patients. Anticoagulation, if safe, can help reduce stroke risk during a period of increased stroke recurrence rate in selected populations.
In this study, the authors designed a single-arm treatment trial to assess the safety of dabigatran initiated within 24 hours of ischemic stroke in patients without AF. Patients with National Institutes of Health Stroke Scale (NIHSS) less than 3 were screened and only included if magnetic resonance imaging (MRI) revealed diffusion restriction. All patients underwent MRI at baseline, 7, and 30 days assessing for ischemia and hemorrhage.
53 patients were enrolled with a median NIHSS of 1 and median infarct volume of 0.8mL. Three patients had evidence of asymptomatic hemorrhagic transformation on MRI at day 7. In 2 of these patients, petechial hemorrhage was evident at baseline and remained unchanged. However, there was one patient death of unknown etiology. There was no incidence of systemic bleeding or recurrent ischemic stroke but 7 patients had asymptomatic diffusion restriction at day 7. The most common stroke etiology was cardioembolism as 15 patients were identified to have AF.
While dabigatran cannot be recommended for use in this setting based on this small non-randomized trial, this trial does suggest the feasibility and safety of dabigatran use in minor stroke within 24 hours of infarct and supports a design for a future randomized trial. The authors suggest short-term use of AC following minor ischemic infarct in all patients while stroke etiology investigation is underway. This strategy would expose patients without AF to unnecessary hemorrhage risk, albeit short term. Future trials should focus on patients with AF and also assess timing of anticoagulation as this is a continuing dilemma in clinical practice.