American Heart Association

Conference

ESOC: Official Welcome & Large Clinical Trials

European Stroke Organisation Conference
May 22–24, 2019

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

The 5th European Stroke Organisation Conference (ESOC 2019) has opened with a fantastic session in Milan on Wednesday! The conference was opened by ESO President Bart van der Worp, Conference Chair Jesse Dawson, and Chair of the Local Organising Committee Danilo Toni, who welcomed over 5,500 participants from 94 countries to the conference, which has doubled in size since inception over the last four years.

Ten landmark studies were presented at the official welcome. Key highlights include results from RESTART, which answers whether to start or avoid antiplatelet therapy after ICH in patients taking antiplatelets for the prevention of occlusive vascular disease. Remarkably, restarting antiplatelet therapy does not increase major haemorrhagic events. In contrast, restarting antiplatelet therapy may reduce recurrent ICH and protect against recurrent major vascular events. This provides reassuring evidence on restarting antiplatelet medication for secondary prevention of occlusive vascular disease in patients with ICH.

RESILIENT demonstrates the overwhelming efficacy of mechanical thrombectomy persists when implemented in the challenges of a developing country healthcare system such as Brazil. In this setting, thrombectomy decreases disability with a number needed to treat of only 6.6, has low complication rates and no increase in symptomatic ICH compared to medical therapy. We must now ensure the tremendous benefits of thrombectomy are available to more patients globally, including developing countries. 

ISC 2019: Acute Endovascular Treatment Oral Abstracts III

International Stroke Conference
February 6–8, 2019

Deepak Gulati, MD

There is uncertainty about factors affecting collaterals, natural course of collaterals and the type of anesthesia during thrombectomy. The session started with the detailed analysis of the GOLIATH trial to identify predictors of collateral circulation grade, infarct growth at 24hrs and the effect of collaterals on clinical outcome. The GOLIATH trial was a single center RCT comparing GA vs CS in acute patients with ELVO within 6 hours. Successful reperfusion was better in GA vs CS (76.9% vs 60.3, p=0.04). This study categorized Grade 2 ASTIN Collateral grading into 2- and 2+ based on <50% or >50% defect in ischemic territory, respectively. The anesthesia protocol included MAP>70 but could not be achieved in 26% of the entire population (35.4% in GA vs 15.9% in CS). Patient were also found to be hypocarbic with median ET CO2 of 33mmHg. There is no effect of collaterals noticed on clinical outcomes. Infarct growth is found to be associated with the use of pressor use (phenylephrine). This study concluded that sedation induced intraprocedural BP drop has a deleterious effect on collateral circulation and may not be reversed by IV pressor administration.

ISC 2019: Opening a Window and Throwing Out the Clock

International Stroke Conference
February 6–8, 2019

Session: “Extending the Thrombolytic Time Window to 9 Hours for Acute Ischemic Stroke using Perfusion Imaging Selection – The Final Result”

Kara Jo Swafford, MD

Henry Ma, PhD, from Monash University in Melbourne, Australia, presented the final results of the EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial at the 2019 International Stroke Conference in Honolulu, HI, on Friday, February 8. The EXTEND trial was a randomized, multicenter, double-blinded, placebo-controlled phase III trial of intravenous alteplase versus placebo designed to test the hypothesis that the time window for treatment could be as long as 9 hours from stroke onset (including wake-up stroke patients with unknown last known well). Recruitment for the EXTEND trial halted in June 2018 after the WAKE-UP trial demonstrated benefit from imaging-guided intravenous thrombolysis in acute stroke patients with unknown last known well. The WAKE-UP trial used MRI rather than CT perfusion for patient selection.

ISC Session: “Medical Therapy for Symptomatic Carotid Stenosis: Time for Modern Data”

International Stroke Conference
February 6–8, 2019

Deepak Gulati, MD

There has been significant improvement in medical management in the last decade leading to various options in 2019 as compared to the era when earlier clinical trials on carotid stenosis were performed.

Dr. Seemant Chaturvedi from the University of Maryland presented on multi-modal treatment of carotid stenosis. Statins plays an important role by reducing LDL being the primary focus of treatment. In the SPARCL study, 32% risk reduction was seen with statins. The cardioprotective mechanisms of physical activity includes psychological, anti-arrhythmic, anti-thrombotic, anti-atherosclerotic and improved hemodynamics. Various studies/guidelines support the encouragement of regular exercise as a stroke prevention strategy and should be emphasized to patients. Physical activity is often found to be a ‘neglected prescription.’ Exercise volumes of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic exercise further reduce CVD mortality. Several diets have been proposed for CV risk reduction, including the DASH diet and Mediterranean diet. Being DM as one of the major vascular risk factor, stroke physicians should be aware of recent advances in anti-hyperglycemic drugs. Some newer antihyperglycemic agents have an FDA indication for reduction of either CV death or CV events. The use of dual antiplatelet therapy has been increasing based on the CHANCE and POINT trial. Some of the newer strategies include PCSK9 inhibitors, ezetimibe and TG reduction. Our current management of symptomatic carotid stenosis is based on the NASCET trial published in 1991. Given the recent advances in multimodal medical treatment, there appears to be a strong need of new clinical trials in patients with carotid stenosis.

ISC Session: “What’s Old Is New Again: Neuroprotection for Stroke in 2019”

International Stroke Conference
February 6–8, 2019

Robert W. Regenhardt, MD, PhD
@rwregen

Moderators: Jean Claude Baron, Andrew Demchuk

The first talk, by Nerses Sanossian, was titled “Neuro-protection in the Pre-hospital Setting.” Sanossian began by introducing the ischemic cascade in which there are rapid changes over minutes to hours (O2 depletion, energy failure, terminal depolarization, ion homeostasis failure), secondary changes over minutes to days (excitotoxicity, SD-like depolarizations, disturbance of ion homeostasis), and delayed changes over days to weeks (inflammation, apoptosis). While no neuro-protective agent has proven successful in phase 3 clinical trials, he asserts that these agents still hold promise. Reconsideration of mechanistic targets is important as there has been a shift in treatment paradigm with thrombectomy now the priority for LVO strokes. As these patients are collected from locations of symptom onset, transported to thrombectomy capable hospitals, and admitted for acute care, when is the best time to offer a neuro-protective agent? Future trials must balance the timing against the cost. An agent could be administered pre-hospital, post-arrival/pre-imaging, post-tPA, pre/during transfer if needed, pre-thrombectomy, or post-thrombectomy. There are unique considerations for each timepoint. In the pre-hospital setting, consent can be difficult, there is no imaging available, agents should be safe in ICH, have no interaction with tPA, easily stored in ambulances, administration should be easy (avoid pumps and compounding), agents should be effective despite fewer patients recanalizing, and have robust experimental data at early time points. In-hospital initiation allows standard consent, imaging is available (could tailor agent to stroke subtype), pharmacies can store and dispense agents, agents can be combined with recanalization (improved delivery to target tissue and opportunity for targeting reperfusion injury and hemorrhagic transformation), and patients can be more carefully selected after imaging for those most likely to benefit.

ISC Session: “Stroke, Anticoagulants and Antidotes”

International Stroke Conference
February 6–8, 2019

Kat Dakay, DO

As direct oral anticoagulants have gained increasingly widespread use and expanding indications, there has been a growing interest in their efficacy, pharmacokinetics, and reversal. At ISC 2019, an invited symposium focusing on this topic was co-moderated by Dr. Bruce Ovbiagele, MD, MSc, MAS, MBA, from USCF and Dr. Kazunori Toyoda, MD, from the National Cerebral and Cardiovascular Center in Osaka, Japan.

Pictured from left to right, speakers and moderators of the “Stroke, Anticoagulants and Anti-dotes” session at the International Stroke Conference, are: Dr. Kazunori Toyoda, Dr. David Seiffge, Dr. Ashkan Shoamanesh, Dr. Maurizio Paciaroni, Dr. Bruce Ovbiagele, and Dr. Truman Milling.

Pictured from left to right, speakers and moderators of the “Stroke, Anticoagulants and Antidotes” session at the International Stroke Conference, are: Dr. Kazunori Toyoda, Dr. David Seiffge, Dr. Ashkan Shoamanesh, Dr. Maurizio Paciaroni, Dr. Bruce Ovbiagele, and Dr. Truman Milling.

ISC Session: “Cost Effective Stroke Interventions in Low and Middle Income Countries” — Left Behind or a Different Reality?

International Stroke Conference
February 6–8, 2019

Victor J. Del Brutto, MD

I had the pleasure to attend the session “Cost Effective Stroke Interventions in Low and Middle Income Countries” moderated by Dr. Salvador Cruz-Flores during the International Stroke Conference held in Honolulu, HI, last week.

Dr. Sheila Martins, founder of the Brazilian Stroke Network, initiated the session, sharing her experience on the implementation of dozens of stroke centers across Brazil as part of a National Stroke Project, as well as the accomplishment of stroke telemedicine, rehabilitation programs and initiatives to increase stroke awareness among the population. Martins emphasized the mortality reduction achieved by such government policies, as well as the future expectations of creating systems able to deliver acute endovascular therapies and establishing a national stroke registry.

ISC: Report on a Positive Study of the EXTEND Trial

International Stroke Conference
February 6–8, 2019

Richard Jackson, MD

I’m writing to you from ISC reporting on an important breakthrough in the hyperacute treatment of ischemic strokes. Dr. Henry Ma reported on a positive study of the EXTEND trial evaluating extending the thrombolytic time window to 9 hours for acute ischemic stroke using perfusion imaging selection.

This was a trial performed in Australia, New Zealand, and Thailand using MRI or CT based perfusion-mismatch with inclusion criteria of  a core <70 mL and a mismatch >10 mL.  The median NIHSS was 11 with a median last known normal (LKN) of 10 hours, median core infarct of 4 mL, and median mismatch of 79 mL.  10% of the of patients had LKN of 4-6 hours, 25% 6-9 hours, and 65% wake up stroke.  72% of the patients had an LVO but did not receive thrombectomy. Despite this, there was a RR 1.44 for MRS 0-1 at 1 month and RR 1.4 for MRS 0-2 at 3 months. There was a RR 2.6 for early improvement in the NIHSS 0-8 points and 51% had 90% recanalization and reperfusion with no difference in death at 90 days. There was a comparable ICH ratio to previous trials with 6% but a RR of 6.9 which did not negate the clinical benefit.

This is a great step towards advanced imaging evaluation of ischemic lesions and reperfusion. One which we have all thought about and been waiting for.

ISC Session: “One Size Fits All? Models for Thrombectomy Systems of Care”

International Stroke Conference
February 6–8, 2019

Robert W. Regenhardt, MD, PhD
@rwregen

Moderators: Carmelo Graffagnino, Edward Jauch

The first talk, “Challenges in Patient Access,” by Carmelo Graffagnino discussed the system problems we face in the thrombectomy era. There are many system models that can be used to organize a region for the care of acute stroke patients. The models that worked well in the past allowed rapid access to tPA, but as thrombectomy expertise is a scarcer resource, there are new challenges. Graffagnino described two cases: one that showed how the system can work perfectly and another that highlighted limitations as a patient experienced severe delay in transferring to the thrombectomy capable center. Some of these limitations are difficult to predict and even more difficult to fix from the perspective of physicians, such as lack of helicopter and ambulance availability.

ISC Session: “Stroke Telehealth: Controversies and Solutions”

International Stroke Conference
February 6–8, 2019

Deepak Gulati, MD

During the joint symposium on the last day of the ISC 2019 on Telestroke, multiple experts with different backgrounds addressed the challenges associated with Telestroke. Telestroke turns 20 in 2019, which reflects 2 decades of progress. It was more of proof of concepts in early 2000 while showing benefit of Telestroke in rural areas. Telestroke plays a predominant role in the ‘Drip and Ship’ model in the United States, whereas the focus has been on Telestroke-supported stroke units in Europe. In the U.S., the Congress also authorized the payment for Medicare FFS Telestroke regardless of patient location in the “Furthering Access to Stroke Telemedicine” FAST Act. The future of Telestroke research will be on value (~quality/cost) vs churn, true econometric analyses, adoption within health system, scalability, disparities in access, continuum of care and Telestroke on call expertise vs AI. Based on data provided, there appears to be a connection between door-to-needle time with the number of consults from spoke hospitals. 50% of the Telestroke consults are usually acute stroke, and the rate of IVtpa administration increases with the number of consults performed. It’s expected to have the involvement of artificial intelligence in the future to deal with increasing demand of Telestroke.