Role of recombinant tissue plasminogen activator in the updated stroke approach

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1 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

2 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 NS 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

3 Outline Routine use of recombinant tissue plasminogen activator Intermediate cases Within the framework of endovascular stroke therapy

4 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.

5 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

6 Helsinki model (Meretoja, Neurology 2012)

7 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)

8 Meta-analysis of rt-pa-based Thrombolytic Trials NINDS, ATLANTIS, & ECASS TRIALS Lancet 2004;363:

9 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

10 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%

11 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: Copyright American Heart Association, Inc. All rights reserved.

12 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)

13 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?

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15 Benefit of pre-treatment of IV TPA has not been consistent but statistical power limited -EXTEND IA required IV TPA

16 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%

17 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 (NCT ), role for IA remains unclear (Yeung, Interv Neurol 2015)