5 Reasons ISC18 Will Be Remembered as a Milestone Stroke Meeting

By M. Shazam Hussain, MD

Even before the last of its presentations ended, the 2018 International Stroke Conference (ISC18), held January 24-26 in Los Angeles, was looking to be one of the most influential conferences in the cerebrovascular field in years. As a meeting attendee, I can attest that important and practice-changing studies were being presented left and right.

For those who didn’t have a chance to attend, this post recaps five developments at ISC18 that will be shaping stroke and cerebrovascular care for years to come.

1) DEFUSE 3 results confirm lengthened thrombectomy window

The conference highlight was the presentation of the DEFUSE 3 trial (simultaneously published in New England Journal of Medicine), a randomized controlled investigation of mechanical thrombectomy in patients 6 to 16 hours after their last known well time. On the primary end point of modified Rankin scale score at 90 days, thrombectomy plus medical therapy was associated with a highly significant 3.4 adjusted odds ratio for a favorable outcome relative to medical therapy alone. The resulting number needed to treat to achieve functional independence was 2.

These results represent the strongest effect of mechanical thrombectomy to date and confirm the earlier DAWN trial, which showed similar benefit from thrombectomy in patients 6 to 24 hours after their last known well time. Although the patients in both trials were very carefully selected, it appears that patients with a favorable imaging profile — i.e., small core, large area of tissue at risk/perfusion abnormality — stand to benefit substantially from mechanical thrombectomy with an acceptable safety profile. Fuller discussion of DEFUSE 3, for which Cleveland Clinic was a participating site, is in this Consult QD post.

2) New guidelines for early care of acute ischemic stroke

In the wake of the DEFUSE 3 results came the meeting’s other huge — and related — news: release of the new 2018 guidelines for early management of patients with acute ischemic stroke from the American Heart Association/American Stroke Association. In response to DEFUSE 3 and DAWN, the recommendation for mechanical thrombectomy was extended to 24 hours, with I-A support for use within 6 to 16 hours and IIa-B support for use within 16 and 24 hours. The indications for mechanical thrombectomy within the 0- to 6-hour window were also broadened.

While the above changes were well received in the ISC18 conference hall, other aspects of the guidelines were more controversial, such as:

• The minimalistic approach of recommendations for evaluating stroke patients outside the acute treatment phase, with designations of “no benefit” for the use of MRI, intracranial vascular imaging (intracranial CTA or MRA) and echocardiography
• The failure to recommend hospital bypass for patients with emergent large vessel occlusion (ELVO)
• The prescriptive nature of imaging recommendations for evaluating and selecting patients with ELVO for thrombectomy in the 0- to 6-hour and 6- to 24-hour windows

Stay tuned for ongoing debate over these and other issues raised by the new guidelines.

3) EXTEND-IA TNK puts tenecteplase on the map for pre-thrombectomy thrombolysis

The Australian EXTEND-IA TNK trial randomized 202 patients with emergent large vessel occlusion (ELVO) to either IV tenecteplase (TNK) or IV tissue plasminogen activator (tPA) before being taken for potential mechanical thrombectomy. TNK showed better recanalization rates (22 percent vs. 10 percent, P = .02), based on cerebral angiogram performed at the hospital where intervention was planned, as well as improved outcomes (odds ratio = 1.7; P = .037) at 90 days after stroke. Safety was comparable between the two thrombolytics. These findings require confirmation in larger trials, but the recanalization rate with tenecteplase is impressive for an IV medication in this most severe stroke subtype. Tenecteplase is currently FDA-approved for use in myocardial infarction.

4) COMPASS: Direct aspiration and stent retrievers comparable for thrombectomy

The eagerly awaited COMPASS trial provided a head-to-head randomized comparison of direct aspiration and stent retriever technology as initial mechanical thrombectomy strategy among 270 patients. It found that the two techniques yielded similar rates of grade 2b or 3 recanalization on the Thrombolysis in Cerebral Infarction (TICI) scale, with direct aspiration meeting the study’s criteria for noninferiority. Clinical outcomes were also similar between the two groups. These data confirm that both techniques are acceptable for interventional treatment of large vessel occlusions, although the overall recanalization rate of approximately 70 percent leaves room for new device technology to address continuing unmet needs.

5) The other COMPASS: Time to rethink secondary prevention strategy?

A second trial named COMPASS was presented at ISC18 — specifically, a subanalysis of the COMPASS trial published in the New England Journal of Medicine last fall that compared cardiovascular events with rivaroxaban plus aspirin versus aspirin alone among patients with atherosclerotic disease. This subanalysis focused exclusively on stroke outcomes in the COMPASS cohort and found that combination therapy reduced ischemic stroke compared with aspirin alone, yielding an absolute risk reduction of 2.7 percent without significant increased risk of major hemorrhage. This raises interesting new questions about the optimal secondary prevention strategy for stroke in patients with atherosclerotic disease.

Dr. Hussain (hussais4@ccf.org) is Director of Cleveland Clinic’s Cerebrovascular Center. Follow him on Twitter: @shazamhussain.