February 19, 2016
Another standing room only session at the ISC 2016, the Stroke Controversies: Debate was a spirited back and forth session exploring three topics of clinical equipoise between thought leaders in their respective fields, of which there are no easy answers.
 
Debate #1: Should we bypass primary stroke centers (PSC)? Arguing in favor, Dr. Goyal points out that tPA does not work very well for proximal large vessel occlusions, the NNT is as low as 2.6 for endovascular therapy, time is brain and we lose time (and therefore brain) transferring from a PSC to a comprehensive stroke center (CSC). Dr. Johnston agreed that in some cases, i.e. if the patient does not qualify for tPA, it may be reasonable, but endovascular treatment is only proven safe and efficacious for a minority of patients. As of now, there is no way to effectively screen patients in the field, and bypassing a PSC may in these situations delay treatment with tPA.

I interpreted this as a debate between pragmatism and idealism. The ideal might be bypassing a PSC, but pragmatically, within our current system of stroke care, this may lead to saving time for a subset of patients with large vessel occlusion at the expense of delaying tPA for the majority of patients, especially within the context of the resources that we have. We need a better work flow to minimize delays in transfers if we continue to rely on PSCs, or alternatively, better screening measures in the field if we want to bypass them.

Debate #2: Embolic stroke, atrial fibrillation, and cerebral microbleeds: Is there a role for anticoagulation? Dr. Diener presented the pro side, arguing that afib increases the risk of stroke and while some microbleeds, such as with amyloid angiopathy, may be a contraindication, others are markers of small vessel disease. NOACs have a more favorable profile for ICH than warfarin and has been demonstrated to not increase microbleeds. Dr. Greenberg, however, iterated the dismal outcome of anticoagulation related ICH (up to 50%), and pointed out that microbleeds lead to 5 ICH events/100 person years. A decision analysis modeling the risk/benefit ratio of anticoagulation has previously identified an ICH risk of 1.4% as the tipping point where risk of anticoagulation outweighed benefits.

There is no easy resolution to this debate. With safer NOACs being introduced, it would seem reasonable to anticoagulate, even in the presence of microbleeds. In parallel, as treatments of ICH continue to advance, the mortality of anticoagulation related ICH will hopefully decline to the point where we will no longer fear it.

Debate #3: Should we assess the outcome of severe strokes early (3 months) or late in clinical trial? Both Dr. Dawson, who argued in favor of an early assessment, as well as Dr. Broderick, who argued in favor or a late assessment, used data from the MISTIE II and IMS III to support their points, which perhaps points to the true equipoise in this question. Dr. Dawson’s point was that in general, the longer a trial is conducted, the more confounders are introduced and often, additional time does not add information that significantly changes the interpretation of the results. Given the resources available, a better approach may be to recruit more patients within a shorter trial rather than follow less patients for a longer time frame. Dr. Broderick argued that especially with severe strokes, there are patients who recover later, and delayed follow up allows for better cost effect analysis.

Much like the first debate, some of this is a question of what is practical vs what is ideal. Delayed recovery is still important for the patient and the physician, and a later assessment allows us to fully capture all of these patients; it will allow us to answer the question of the sustainability of recovery. However, with limited funds for trials, it may be difficult to implement this. 

– Peggy Nguyen, MD