Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation 
Interview Conducted by Chirantan Banerjee, MD

Dr. Banerjee: Tell us about the key findings from your recent article in Stroke.   

Dr. Butcher:The key findings are that acute treatment with the Direct Oral Anticoagulant (DOAC) dabigatran within 24 hours of an acute ischemic stroke is feasible. Given the small sample size, we have not definitively proven safety of course, but the lack of symptomatic hemorrhagic transformation, and indeed the paucity of even subclinical HT on susceptibility weighted MRI, is encouraging. Certainly we saw no safety signal that would preclude pursuing this approach in a larger study, as we are currently. 

Dr. Banerjee: What prompted you and your co-authors to perform this study? 
Dr. Butcher: It is now recognized that early recurrent stroke after TIA/minor stroke is a frequent problem and new treatment target. Efforts to date have focused on anti-platelet approaches (CHANCE, POINT, SOCRATES). However, it has also been shown that occult paroxysmal AF is common in this population (CRYSTAL AF and EMBRACE). Thus, many patients with acute minor stroke/TIA will not benefit from anti-platelet approaches. 
What has prevented routine anticoagulant use in the past is that any benefits were outweighed by increased hemorrhagic complications (primarily symptomatic HT). These studies were done with heparin/LMWH. Dabigatran, in the RE-LY trial had an intracranial hemorrhagic complication rate that was comparable to ASA. Thus, there appeared to be an opportunity to protect patients from all potential recurrent thromboembolic events, without increasing the risk of HT or other hemorrhages. Our rationale for 30 days of treatment was that this is the period of highest stroke recurrence. We aimed to protect patients during this high risk period, but also give clinicians time to determine which patients had potential cardiac sources of embolism (TTE, Holter). 
Dr. Banerjee: Tell us about the biggest challenge you came across while conducting this study. 
Dr. Butcher: There were really three:
1. The first was actually convincing some of our colleagues that hyper acute DOAC use was a reasonable concept. There was initially some trepidation on the part of some of our colleagues.
2. All patients needed an MRI scan before treatment, all within 24 hours. Even in a research center such as ours, this was a challenge. 3. Finally, there were competing trials that made enrollment a challenge (POINT and SOCRATES). 
Dr. Banerjee: What are the major implications of this work?  
Dr. Butcher: The implications are that it may be reasonable to protect all patients with minor stroke, using dabigatran. Of course, this needs to be tested in a larger RCT. This is what we are doing now, with DATAS II, which randomizes 300 patients to ASA or dabigatran for 30 days.   
The findings also support the safety of the approach being tested in the ESUS trials, one of which uses dabigatran. The difference between these trials and ours is that we do not make the assumption that all subcortical strokes are not embolic—some may therefore benefit from acute DOAC therapy. These patients are excluded from ESUS trials. In addition, the short term nature of the therapy, combined with a more extensive cardiac interrogation may lead ultimately to more selective therapy with DOACs. Each approach has its merits. A small study like DATAS supports the safety of both.  
Dr. Banerjee: What do you plan to do next, based on these current findings?  
Dr. Butcher: We are currently conducting DATAS II, as described above.  
Dr. Banerjee: What do you like to do in your free time? 
Dr. Butcher: I spend time with my kids. We all like to ski in the winter (cross country and downhill). I also play hockey (badly) and enjoy triathlon when time permits.