Role of recombinant tissue plasminogen activator in the updated stroke approach Joshua Z. Willey, MD, MS Assistant Professor of Neurology Division of Stroke, Columbia University October 2015 jzw2@columbia.edu
Disclosure Information Relationship with companies who manufacture products used in the treatment of the subjects under discussion Yes No x If "Yes," list company(ies) with the relationship(s) below. Relationship Research Support Speaker's Bureau Consultant Share Holder Other Financial Support Large Gift(s) Manufacturer(s) NIH/NINDS: K23 NS073104 Local investigator for POINT (NIH), SOCRATES (Astra /Zeneca) and PRISMS (Genentech) None Heartware incorporated None Honoraria from American College of Physicians for MKSAP 17 None Relationships with any of the commercial supporters of this CME activity: N/A Discussion of unlabeled uses: Yes _x No -Use of intra-arterial tpa for acute stroke, and IV beyond 3 hrs
Outline Routine use of recombinant tissue plasminogen activator Intermediate cases Within the framework of endovascular stroke therapy
What is a stroke code? Pre-notification Stroke page pre or post arrival On arrival: History Neurological Examination Neuro-imaging DTN < 60, < 45? Balami JS, et al. The exact science of stroke thrombolysis and the quiet art of patient selection. Brain 2013.
The stroke code Accuracy of stroke codes not widely known, poor sensitivity and specificity (sepsis, migraine, conversion) Greatest source of delays: imaging to treatment time Getting a history Consent or Assent Determining eligibility
Helsinki model (Meretoja, Neurology 2012)
Acute Management of Stroke Only FDA-approved treatment for acute ischemic stroke remains IV tpa Few get it or have access to it (Kleindorfer, Stroke 2009) 64% of hospitals do not give tpa 40% of the population lives in counties where < 3% get tpa Delays in thrombolysis lead to increased mortality, hemorrhage; per 15 minutes OR 0.96 for both (Saver, JAMA 2013)
Meta-analysis of rt-pa-based Thrombolytic Trials NINDS, ATLANTIS, & ECASS TRIALS Lancet 2004;363:768-74.
Slowing down DTN Multi-modality imaging slows DTN and decreases DTN < 60 (Garcia-Pastor, J Neuroimag 2015; Noorian, J Stroke CVD 2014) Performing angiography or perfusion imaging doubled in-hospital delays (Meretoja, Neurology 2012) Can be performed in a timely manner at some centers but requires large learning curve
Endovascular therapy The benefits of endovascular therapy has been well established now and is standard of care Selected patients: require multi-modality imaging The use of advanced imaging beyond NCCT should not delay thrombolysis (McTaggart, JNIS 2015) How many patients are eligible for endovascular therapy? Surprisingly hard to find Conservatively 2%
Temporal trends in the use of endovascular therapy within hospitals participating in Get With The Guidelines-Stroke (GTWG-Stroke) during the past decade. Bijoy K. Menon et al. Stroke. 2015;46:989-995 Copyright American Heart Association, Inc. All rights reserved.
Endovascular therapy Get with the guidelines stroke (Menon, Stroke 2015) 9506 endovascular, of which 3210 IV/IA 47,333 IV alone Among hospitals providing treatment routinely (99 hospitals) Treated a mean of 6 patients per year Median proportion of 2.6% Stroke subtypes: large vessel syndromes most likely in the elderly (Nacu, Acta Neurol Scand 2015)
Treatment beyond 3 hours MR CLEAN (NEJM 2014): all outcomes favored INR treatment - ~ 90% tpa before Inclusion: intracranial occlusion, NIHSS 2 or more Baseline: ASPECTS 9, most non-disabled, 85% M1 and ICA T occlusions Similar inclusion criteria and results in EXTEND- IA, ESCAPE, SWIFT-PRIME (NEJM 2015) Proportion screened for the trial?
Benefit of pre-treatment of IV TPA has not been consistent but statistical power limited -EXTEND IA required IV TPA
Endovascular alone? SYNTHESIS (NEJM 2013) IV TPA versus endovascular therapy Clear difficulty with device being used No difference in outcomes 30.4% vs 34.8% ICARO-3 (Paciaroni, J Neurol 2015) Acute ICA occlusion randomized mrs 0-2: 27.4% vs 32.4% sich: 37% vs 27.4%
Acute Basilar Thrombosis BASICS: prospective observational registry of acute basilar artery occlusion (n = 619) (Schonewille, Lancet Neurol 2009) 183 got anti-thrombotics, 121 IV tpa (+/- IA tpa), and 288 with IA treatment 68% had a poor outcome (mrs 4-6), and no treatment appeared superior Severe deficit patient (coma, locked in): IV tpa and IA treatment had similar success 0/41 severe patients after 9 hrs had a good outcome Clinical trial underway (NCT01717755), role for IA remains unclear (Yeung, Interv Neurol 2015)