The American Heart/Stroke Associations’ 2018 International Stroke Conference (ISC) has come to a close after an exciting week of new data and guidelines which are changing the field of stroke and cerebrovascular disease. With nearly 5,000 attendees from all around the world, there were plenty of great presentations and discussions around a broad range of topics including pre-hospital care and triaging, acute stroke therapy, stroke evaluation and management and rehabilitation.
DEFUSE 3 and DAWN: Extending Acute Stroke Therapy to More Patients
The highlight of the conference was the presentation of the DEFUSE 3 trial1, a randomized controlled study evaluating mechanical thrombectomy in patients 6–16 hours after their last known well time. On the primary outcome measure of modified Rankin Scale score at 90 days, there was a highly significant 3.4 adjusted odds ratio — equaling a number needed to treat of 2! This is the strongest effect of mechanical thrombectomy in a trial to date. These results confirm the results of the previously published DAWN trial2 which showed similar benefit in patients 6–24 hours after their last known well time. It should be noted that patients in these trials were very carefully selected, but patients with a favorable imaging profile (small core, large area of tissue at risk/perfusion abnormality) can benefit greatly from mechanical thrombectomy with a reasonable safety profile.
Multiple Additional Positive Studies Presented
There were many great presentations and new data presented over the three day conference. Perhaps the study which generated the most interest was the EXTEND-IA TNK study. In this Australian study, patients with emergent large vessel occlusion (ELVO) received either intravenous tenecteplase (TNK) vs. intravenous tissue plasminogen activator (tPA) before being taken for potential mechanical thrombectomy. TNK showed better recanalization rates (22% vs. 10%, p=0.02) based on cerebral angiogram performed at the hospital where intervention was planned to be performed and improved outcomes (Odds ratio 1.7, p=0.037) at 90 days post stroke. While these results need to be confirmed in larger trials, the recanalization rate is impressive for an intravenous medication in this most severe stroke subtype.
The COMPASS trial assessed a hot topic in the field of neurointervention — a head to head comparison of direct aspiration and stent-retriever technology for mechanical thrombectomy. Both techniques showed similar TICI 2b/3 rates, with direct aspiration meeting the study’s criteria for non-inferiority. Outcomes were also similar between the two groups. This data confirms that both techniques are acceptable for interventional treatment of ELVO, though the overall recanalization rate of ~70% leaves room for new device technology to continue to be developed.
A second trial also by the name of COMPASS3 was presented — this study assessed rivaroxaban and aspirin versus aspirin alone in patients with atherosclerotic disease, particularly focusing on the stroke subgroup. The combination therapy reduced ischemic stroke with an absolute risk reduction of 2.7% without significant increased risk of major hemorrhage. This raises interesting new questions about the best secondary prevention strategy in stroke patients with atherosclerotic disease.
The PRINCE study from China added new information about treatment strategies for transient ischemic attack (TIA)/minor stroke, comparing ticagrelor + aspirin vs. clopidogrel vs. aspirin in this population. Patients on the ticagrelor/aspirin arm showed reduced platelet reactivity over the course of the 90d study, and there was a trend toward reduced recurrent stroke, though this was not statistically significant. Further study of this strategy in this high risk population will be interesting.
The final results of the WEAVE study were also presented. Following the results of the SAMMPRIS trial showing high complication rates and worse outcomes for patients with intracranial atherosclerotic disease (ICAD) treated by stenting compared to medical therapy, it was noted that patients in that trial were treated off-label to the approved indication for the Wingspan stent system, and that prior on-label trials showed much lower complication rates. This study followed stringent, on-label indications for stenting and confirmed a very low complication rate of only 2.6% (vs. 14.1% in SAMMPRIS). In patients where protocol violation occurred and patients were treated off-label, a much higher complication rate (23.9%) was seen. In particular, it appears that patients treated <7 days are at especially high risk. This data will help to inform stroke specialists and neurointerventionalists about the proper application of stent therapy in the ICAD population.
New Guidelines for the Early Management of Patients with Acute Ischemic Stroke Released
The most anticipated presentation of the meeting was the release of the new 2018 guidelines for the Early Management of Patients with Acute Ischemic Stroke4. It also turned out to be the most controversial part of the meeting.
The recommendation for mechanical thrombectomy was extended to 24 hours (6–16 hours, level 1A; 16–24 hours, level IIa-B) and in the <6 hour window, the indications for mechanical thrombectomy were also relaxed. This was met with general agreement and appreciation. However, other recommendations including not recommending hospital bypass for patients with ELVO, the prescriptive nature of the imaging recommendations for evaluation and selection of patients with ELVO in the <6 hours and 6–24 hour windows among others raised concern for many in attendance. The most debated section, though, was the recommendations for evaluation of stroke patients outside of the acute phase of treatment. A minimalistic approach with recommendations of “no benefit” were given to use of MRI, intracranial vascular imaging (intracranial CTA or MRA) and echocardiography, raising great concern from a large number of attendees both in the official question and answer session as well as around the convention center. It appears there will be a great deal of further debate and discussion about these new guidelines in the months to come.
Overall, this year’s International Stroke Conference will be remembered as one of the most impactful and memorable conferences in stroke care for the last few years. Greatly impactful studies and data were presented, which will set the course for the cerebrovascular disease field for years to come. These, along with the new guidelines and the debate which will rage on, will make this an exciting area to watch for the foreseeable future.
M. Shazam Hussain, MD, FRCP(C)
Director, Cerebrovascular Center
Associate Professor, Cleveland Clinic Lerner College of Medicine