Thrombolytics and Beyond
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- Mervyn Hawkins
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1 Thrombolytics and Beyond Greenville Memorial Rodney Leacock MD
2 Introduction 795,000 strokes per year in the US 87% ischemic 13% hemorrhage, 3% SAH Fourth leading cause of death - was third Mortality rate has decreased by 34.8% Leading cause of disability Over 7 million stroke survivors South Carolina is 4th in stroke mortality 34.3 billion dollars / year Direct cost 18.8 Billion AHA/ASA Heart and Stroke Statistics 2012: Circulation : 125
3 Sacco et al Stroke 2006 Introduction Stroke An interruption in the blood flow to the brain, spinal cord TIA (transient ischemic attack) a temporary ischemic neurologic deficit of less than 24 hours duration most minutes duration prevalence 5 million ABCD2 score for TIAs 10 % risk of stroke in 2 days 17% risk of stroke in 90 days 1/3 +ve infarction on MRI ACT FAST Medical emergency call 911
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6 Stroke Belt
7 Mobile Care Ambulance Service Stroke Themed Ambulance 40,000 miles/year Provide transport services throughout region
8 TIME IS BRAIN 1.9 MILLION NEURONS LOST PER MINUTE ISCHEMIC BRAIN LOOSES 3.6 YEARS PER HOUR Working against the clock Saver JL Stroke 2006
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12 IV Thrombolysis NINDS trial; NEJM 1995 IV Alteplase (rt-pa) vs placebo; multicenter randomized controlled N = 624 Onset of ictus < 3 hours.9 mg/kg iv Maximum 90 mg 10 % as bolus remainder over one hour
13 IV Thrombolysis rt-pa group significantly better than placebo at 3 months Symptomatic ICH risk 6.4% vs 0.6% Significant Mortality 17% vs 21% FDA approved June 1996
14 IV Thrombolysis With development of Stroke Systems of Care JC PSC (Primary Stroke Centers) JC CSC (Comprehensive Stroke Centers) Public and Professional awareness and education Legislature supporting local, regional, state, and national initiatives and best practices Thrombolytic use is increasing Remains under utilized
15 Stroke Alerts Stroke Alerts Group page/text Neuro CT Lab Pharm PPC Charge nurses (Jan- Sept) Other Sites HMH Greer IP GMH
16 GHS - IV t-pa for Stroke (YTD) GMH Drip & Ship
17 Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Oct-12 Nov-12 Dec-12 Jan-13 Feb-13 Mar-13 Apr-13 May-13 Jun-13 IV tpa Median Times Door to IV tpa Times - Median
18 Relation of onset-to-treatment time (OTT) and excellent final functional outcome (mrs 0 1 at 90 days) for intravenous tissue plasminogen activator (IV TPA). Saver J. Stroke 2012;44: Copyright American Heart Association
19 Telestroke Consult in Action Greer, Hillcrest, Baptist Easley, Laurens, Oconee, Newberry, AnMed
20 Telestroke Door-to- Needle Sep-13 Aug-13 Jul-13 Jun-13 May-13 Apr-13 Mar-13 Feb-13 Jan-13 Dec-12 avg Telestroke Consult Times (Median) 0:24 0:11 0:19 0:11 0:15 0:09 0:19 0:11 0:24 0:15 0:14 0:13 0:26 0:13 0:15 0:22 0:12 0:09 0:18 0:21 0:11 0:17 0:12 0:29 0:27 0:34 0:34 0:32 0:30 0:38 0:34 0:35 0:33 0:07 0:12 0:09 0:18 0:11 0:30 0:16 0:16 0:23 0:08 0:12 0:00 0:30 1:00 1:30 2:00 2:31 Door - GHS SA page Consult start - TPA rec SA Page - consult start TPA rec - TPA admin
21 GHS Goal GHS Median min MUSC Median min Ga Median Door to Consult Request Start to tpa decision Request to Consult Start Decision to tpa start MUSC data from May 2008-April 2011 for 231 pts treated w/ IV tpa. Published March 14, 2012 in Frontiers in Neurology doi: /fneur Ga data from Mar 2011-Nov2012 for 115 pts treated w/ IV tpa. Published online July 9, 2013 in Stroke: Journal of the American Heart Association.
22 PROACT II Second multicenter study to determine the efficacy of IA thrombolysis for MCA occlusion within 6 hours 180 patients were randomized rpro-uk 121;control - 59 Median NIHSS 17; median time to treatment was 5.3 hours Neurological deterioration occurred 11/ 108 (10%) Symptomatic ICH were more commonly seen in patients with baseline NIHSS of 11 or more Immediate recanalization rates rpro-uk 66%; control 18 % At 90 days 40 % of the rpro-uk group and 25% of controls achieved an mrs of 2 or less 25% and 27% mortality respectively Furlan et al. JAMA 1999
23 Recanalization Rates MERCI (2004) 57.3%; 69.5 % with ia tpa adjunct Penumbra (2008) reported 87% or better recanalization rate Solitaire (2011) compared with MERCI 83.3% vs 48.1 % recanalization rate (SWIFT 2012) Pro-ACT II(1999) 57.7% rt-pa (Mazighi et al, Lancet Neurology 2009) 52%
24 Example of thrombolysis in cerebral infarction (TICI) 0 and TICI 2b. Zaidat O et al. Stroke 2013;44: Copyright American Heart Association
25 Example of thrombolysis in cerebral infarction (TICI) 1 and TICI 3. Zaidat O et al. Stroke 2013;44: Copyright American Heart Association
26 Thrombolysis rate (A) and median arrival-tissue-type plasminogen activator (tpa) time (B) by onset-arrival time for each of the 3 groups of thrombolysis volume. Bray B et al. Stroke 2013;44: Copyright American Heart Association
27 Median arrival-scan (A) and arrival-tissue-type plasminogen activator times (B) by hospital annual thrombolysis volume. Bray B et al. Stroke 2013;44: Copyright American Heart Association
28 Violin plot of arrival-tissue-type plasminogen activator (tpa) times by thrombolysis volume. Bray B et al. Stroke 2013;44: Copyright American Heart Association
29 Thrombolytics Any thrombolytic therapy 19.20% 16% 13.20% GMH treatment rates high Time to treatment fast Complication rates low GWTG-Strok: 2013 Jan-Jun GMH All SC Hospitals JC PSC Hospitals Time to Intravenous Thrombolytic Therapy (DTN < 60 min) 90.60% Thrombolytic Complications 5.10% 58.30% 57.50% 2.30% 2.80% GMH All SC Hospitals JC PSC Hospitals GMH All SC Hospitals JC PSC Hospitals
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31 Rates of IV-tPA use within 3 hours of onset over time, in all ischemic stroke cases regardless of time of arrival or any tpa contraindications (solid line) and among fully tpa-eligible AIS patients arriving 2 hours (dashed line). Schwamm L et al. Circ Cardiovasc Qual Outcomes 2013;6: Copyright American Heart Association
32 Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Enhanced Regimen Stroke Trial by Arthur M. Pancioli, Opeolu Adeoye, Pamela A. Schmit, Jane Khoury, Steven R. Levine, Thomas A. Tomsick, Heidi Sucharew, Claudette E. Brooks, Todd J. Crocco, Laurie Gutmann, Thomas M. Hemmen, Scott E. Kasner, Dawn Kleindorfer, William A. Knight, Sharyl Martini, James S. McKinney, William J. Meurer, Brett C. Meyer, Alexander Schneider, Phillip A. Scott, Sidney Starkman, Steven Warach, and Joseph P. Broderick Stroke Volume 44(9): August 26, 2013 Copyright American Heart Association
33 Schematic of blinded administration of recombinant tissue plasminogen activator (rt-pa) plus eptifibatide vs standard rt-pa. Pancioli A et al. Stroke 2013;44: Copyright American Heart Association
34 Ultrasound Identification and Lysis of Clots by Andrei V. Alexandrov Stroke Volume 35(11 suppl 1): November 1, 2004 Copyright American Heart Association
35 Figure 1. Abnormal thrombolysis in brain ischemia (TIBI) flow grades (upper left images), and acute middle cerebral artery occlusion location on magnetic resonance angiography (white arrows) with relative ultrasound transducer position on the skull (white i... Alexandrov A. Stroke 2004;35: Copyright American Heart Association
36 Figure 2. Complete early middle cerebral artery recanalization on power-motion transcranial Doppler and serial NIHSS scores (upper row). Alexandrov A. Stroke 2004;35: Copyright American Heart Association
37 CLOTBUST-Hands Free by Kristian Barlinn, Andrew D. Barreto, April Sisson, David S. Liebeskind, Mark E. Schafer, John Alleman, Limin Zhao, Loren Shen, Luis F. Cava, Mohammad H. Rahbar, James C. Grotta, and Andrei V. Alexandrov Stroke Volume 44(6): May 24, 2013 Copyright American Heart Association
38 A, Operator-independent ultrasound device. Barlinn K et al. Stroke 2013;44: Copyright American Heart Association
39 Conclusion Acute Stroke is a medical emergency Act FAST(ER); Call 911/EMS Intravenous thrombolysis remains most effective therapy for acute ischemic stroke Larger volume centers shorter door to needle times Administration rate is increasing Nearly double over past 10 plus years (4% - 7%) Adjunctive therapies show promise with proven safety
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