American Heart Association

author interview

Author Interview: Ken Butcher, MD, PhD, FRCP(C)

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.
 

World Stroke Day 2015 – “I am Woman”

In recognition of World Stroke Day 2015 and the theme “I am woman”, Stroke interviewed Cheryl Bushnell, MD, MHS, Professor of Neurology, Director at Wake Forest Baptist Stroke Center. Learn more about World Stroke Day

Stroke: World Stroke Day is on Thursday the 29th October 2015. The World Stroke Organization’s theme for World Stroke Day 2015 is ‘I am Woman’. What is the most important message for women when it comes to stroke?
Dr. Bushnell:
The most important message for women is to know what a stroke is, what to do if one is occurring, and how to prevent a stroke. Women have unique risk factors, including pregnancy complications and use of hormones, so they need to know that these are risks of stroke. One of the key messages of our stroke prevention in women guidelines is that women with a history of preeclampsia (high blood pressure during pregnancy plus protein in the urine) are at risk for stroke for up to 30 years after childbirth.

Stroke: Are women at higher risk of stroke?
Dr. Bushnell:
No, if you measure stroke incidence, men are at higher risk. But, because women live longer, they are at higher risk over an entire lifetime. Women have a 20% lifetime risk of stroke after age 55, whereas men have a 17% lifetime risk.

Stroke: How does pregnancy affect a woman’s risk of stroke?
Dr. Bushnell:
Yes, it appears to double the risk of stroke compared to a woman who is not pregnant. This is especially true in the postpartum time period, and applies to most stroke types, including ischemic and hemorrhagic stroke, as well as cerebral venous thrombosis.

Stroke: Does taking birth control pills or hormonal replacement affect a woman’s stroke risk? 
Dr. Bushnell: Yes, birth control pills double the risk of stroke compared to women not taking these pills. However, the absolute risk of a healthy young woman taking these pills is still low. For example, a young woman’s risk of stroke may be 10/100,000, and taking OCPs increases this to 20/100,000. However, if a woman has high blood pressure, high cholesterol, diabetes, obesity, or smokes cigarettes, all of these accentuate the risk of stroke in a woman using OCPs compared to women not taking OCPs. For hormone replacement, older women have about a 40% increased risk of stroke compared to women not taking the drug. It is important to realize these women were at least 10 years past menopause on average. The recent study of women who are recently menopausal (within 5 years), had no significant increase in markers of stroke risk (carotid wall thickening) compared to women not using hormone therapy. Therefore, hormone replacement is not recommended for older women and those with an increased risk of stroke (such as hypertension, diabetes, high cholesterol, prior heart disease).

Stroke: Are women underrepresented in clinical research studies of stroke?
Dr. Bushnell:
Yes, with only a couple of exceptions, women make up 35% to 40% of stroke prevention trials.

Stroke: What can health care providers do to reduce the burden of stroke in women? 
Dr. Bushnell: Improve stroke awareness and what to do, and promote a healthy lifestyle. Women who incorporate the most healthy strategies in their daily lives have a 70% decreased risk of stroke compared to women with none of these strategies. This includes regular physical activity, healthy diet, normal body mass index, moderate alcohol use, and not smoking. Another important strategy is to maintain normal blood pressure. The healthy lifestyle can do this, but women tend to have high blood pressure at older ages, and these women are also less likely to have their blood pressure controlled. Therefore, education about blood pressure in older women is extremely important.

Stroke: A recent study showed that 81% of stroke center directors are men. What can be done to increase the role of women in stroke leadership positions?
Dr. Bushnell:
For those of us in these leadership positions, hopefully we function as role models to promote more women as stroke center directors as a career choice. More women are going into stroke fellowships, so this will take time for the next generation to reach these leadership roles. Given the multidisciplinary nature of stroke centers and the tendencies for women to be collaborative, I believe women are likely to be successful in this role.  

Learn more about World Stroke Day

Author Interview: Valery L. Feigin, MD, PhD




New Strategy to Reduce the Global Burden of Stroke
Interview conducted by Deepa P. Bhupali, MD


Dr. Bhupali: Can you give a brief overview on the tool you developed and address in your article? 
Dr. Feigin:
The Stroke Riskometer was developed with the main purpose of improving primary prevention of stroke on a global level.
The application provides users with their absolute and relative risks of stroke, along with how that risk is modified as their health care profiles change. Users can monitor their results, chart progress, receive education regarding stroke symptoms, and if they choose to, share their information via email with a person of their choice. The application is available on iOS and Android platforms, and there are two versions: the Lite version which is free and the Pro version which can be purchased. The Pro version provides additional information on how to reduce stroke risk, based on one’s individual risk profile, but both versions calculate and identify risk factors, provide stroke education and offer the ability to collect data for research. This research will provide significant epidemiological insights, which are vital to improved prevention and treatment of stroke 



Dr. Bhupali: What prompted you and your co-authors to create this tool?
Dr. Feigin:
Our work grew out of two major observations. First, stroke is a major non-communicable disorder (NCD). Despite decrease in incidence and mortality, the overall number of people affected by NCDs – stroke, MI, diabetes, dementia – is growing. This suggests that primary prevention is not sufficiently effective. If this is not addressed and we carry on with business as usual, the burden will continue to grow.
Secondly, there is a research problem. Despite pushes for epidemiological research for NCDs, the majority of countries don’t have reliable data on frequency, determinants and distribution of stroke and other NCDs. This is not because of a lack of understanding regarding research methodology. The void in data is largely related to the expense of conducting the research. Consequently, without accurate data, we cannot develop evidence based health care, planning and prevention strategies. We hope to address these two major problems — the growing burden and lack of data — with this app. This is what excites us.  

Dr. Bhupali: What is innovative about this work?
Dr. Feigin:
There is currently nothing else comparable to the app’s ability to capture accurate data from around the world. As an example of that, the application will be available in world’s most common languages, giving it the ability to reach the global population. Additionally, we worked very hard on the privacy aspects of this application and have implemented unique strategies to guarantee the security of users’ data and their anonymity, if they consent to participate in data collection.
 

Dr. Bhupali: What is one of the challenges you anticipate in introducing this tool?
Dr. Feigin:
At this time, our main challenge is to let people know that the app is available. We want people to know that there is a tool that will inform them about their absolute and relative stroke risk, provide education regarding stroke symptoms and will monitor their progress and recalculate their stroke risk based on the improvements they seek to make to their health. 

Dr. Bhupali: What is the key take-away message from your article?
Dr. Feigin:
Stroke is highly preventable. It does not happen at random, rather it affects people who are at risk of having a stroke – and these people can reduce their risk.
We implore people to use the app now – learn about your risk factors and how to manage them. Stroke is much easier to prevent than to treat, we want to let people know that they can help prevent stroke and safeguard their health and well-being. 

For more information on Dr. Feigin and the Stroke Riskometer click here.
To read the article in Stroke click here.