Alternatives to CDT: Half-dose Thrombolytics and Mechanical Thrombectomy Thomas Tu, MD FSCAI, FACC The Dawn of A New Era of PE Therapy A Sunrise Pulmonary Embolism Symposium May 22, 2019
Disclosures • None currently • As of July 1, 2019, I will be employed by Inari Medical as Chief Medical Officer
Case Presentation • 68 year old man POD 2 from resection of brain tumor • Acute respiratory decompensation • Intubated on 100% FiO2, Arterial O2 sat 90% • CT demonstrates saddle pulmonary embolism with RV/LV ratio 1.8 • Troponin 1.4, BNP 4500 • His HR is 110, BP 100/60 on low dose levophed • The neurosurgeon states that there is an absolute contraindication to thrombolytic administration in this patient
Contraindications to Thrombolytics Relative: Absolute: • Bleeding diathesis • History of hemorrhagic stroke • Uncontrolled severe • Active intracranial neoplasm hypertension • Recent (<2 months) • Cardiopulmonary resuscitation intracranial surgery or trauma • Nonhemorrhagic stroke within • Active or recent internal prior 2 months bleeding in prior 6 months • Surgery within the previous 10 days • Thrombocytopenia (plts < 100,000)
Why Consider Alternatives to CDT • Contraindications to thrombolytic therapy • Urgent need for restoration of pulmonary blood flow • Patient “ too sick ” to be sent for catheter-procedure • Clinical equipoise about benefits of CDT
Low Dose Thrombolysis of PE Am J Cardiol 2013;111:273-277
MOPETT Conclusions • Half dose thrombolytics seemed to lower pulmonary hypertension and possibly recurrent PE compared to control • Bleeding rates seemed to be acceptably low
Crit Care Med 2018; 46:1617 – 1625
Conclusions from Kiser • 46% of patients treated with half dose t-PA did not require further intervention • A higher percentage of those treated with half dose required treatment escalation compared with full dose • Bleeding rates were similar between doses (~0.5 % ICH, 6-7% ABLA)
Conclusions: Half Dose t-PA • Small studies suggest that it may or may not be as effective as full dose t-PA • Bleeding rates are variable, but catastrophic bleeding still a concern
Mechanical Thrombectomy • Acute clot removal without the risk of thrombolytic administration • Rapid onset of effect • Reduction in patient acuity and post-treatment intensity of care
Penumbra • Indigo System • Adapted from neurointervention
EXTRACT-PE Trial • Evaluating the Safety and Efficacy of the Indigo Aspiration System in Acute Pulmonary Embolism • PI: Dr. Akhilesh Sista • 150 patients • Efficacy Endpoint: RV/LV ratio improvement at 48 hours • Safety Endpoint: Major adverse events • Estimated enrollment completion: Q4 2019
FlowTriever System – First Generation Aspiration Guide Catheter (“AGC”) Fl FlowTriever De Devic ice ( “ FT FT ” ) Retraction Aspirator (“RA”) • Navigates through the right heart • Deployed out of AGC and • Retracts the FT with and delivers FT device to the into thrombus thrombus into the AGC pulmonary artery • Disrupts, engages and • Synchronizes aspiration • Large bore catheter maximizes moves large volume of and retrieval aspiration and collection of thrombus thrombus Dis Disru ruption, mac aceration an and retri rieval of of clot clot In Increased ed lu lumen Rapid id flo flow res estoration R Red educed PA pressure e R Red educed ed RV str train in 21
FLARE Study Overview • Objective • Evaluate the safety and effectiveness of the FlowTriever System for use in the removal of emboli from the pulmonary arteries in the treatment of acute PE • Study Design • Prospective, single-arm, multicenter study • 106 patients, 18 sites • Follow-up at 48-hours & 30-days • Primary endpoints • Effectiveness – reduction in RV/LV ratio at 48-hours • Safety – Composite major adverse event rate 23
Major Adverse Event Definition • Device-related death • Major bleeding (VARC-2 definition) • Treatment-related adverse events: • Clinical Deterioration • Pulmonary vascular injury • Cardiac injury • All endpoints are measured within 48 hrs ± 8 hours
RV/LV Ratio Outcomes RV/LV Ratio All Patients (N=106) 2.00 RV/LV Ratio 1.50 1.53 Reduction 0.39 p <0.0001 1.00 1.15 0.50 0.00 Baseline 48-Hour Baseline 48 Hour Reduction p All Patients (N=106) 1.53 1.15 0.39 p <0.0001 All Paired Patients (N=103) 1.54 1.15 0.39 p <0.0001 Paired Patients w/o Lytic (N=101) 1.54 1.15 0.38 p <0.0001 25
FlowTriever Clot Retrieval Experience, Acute to Chronic ACUTE CHRONIC 26
Clinical Outcomes ICU stay post-procedure, median 1 day 0 = 44 1 = 23 ICU stay: distribution 2 = 18 3+ = 21 Days to discharge post-procedure, median 3 days # Patients lost-to-follow-up 2 # Patients any-cause mortality 1 # MAEs* 4 (ITT 3.8% , mITT 3.8%) 27
Major Adverse Events • No intracranial hemorrhage • No access-site major bleeding • No device-related death • No device-related pulmonary injury • No device-related cardiac injury • One patient had a bleeding event • Three patients had treatment-related clinical deterioration
FLARE Effectiveness in Context Reduction in RV/LV Ratio at N Treatment tPA 48 Hours FlowTriever mechanical FLARE 104 0 mg 0.39 / 25% thrombectomy SEATTLE II (2015) 150 USAT 24 mg 0.42 / 24% ULTIMA (2014)* 30 USAT arm 10-20 mg 0.29 / 22% Becattini et al (2010) 28 Systemic Thrombolytic 30-50 mg 0.31 / 24% Fasullo et al (2011) 35 Systemic Thrombolytic 100 mg 0.40 / 27% Mi et al (2013) 57 Systemic Thrombolytic 50 mg 0.11 / 8% *RV/LV Ratio in ULTIMA measured at 24 hours 29
FLARE Safety in Context Majo ajor In Intr tracrania ial l He Hemorrhage Stu Study Bl Bleedin ing (Fib (Fibrinoly lysis is Gr Group) FLA FLARE 1/ 1/106 (.9% (.9%) 0/ 0/106 (0% (0%) UL ULTIMA (US (USAT ar arm) 0/30 (0% 0/ (0%) 0/ 0/30 (0% (0%) (Kucher, , et al al. 2013 2013) PE PEITHO (tPA ar arm) 58/5 58/506 (11.5 (11.5%) 10/506 (2% 10/5 (2%) (Meyer G, (M G, et al al. 2014 2014) SE SEATTLE II II 17/150 (11.4 17/1 (11.4%) 0/150 (0% 0/ (0%) (Pia (Piazza G, G, et al al. 2014 2014) 30
Evolution of Flowtriever
SpO 2 (%) 100 90 80 70 60 50 40 30 20 10 0 16:59 17:04 17:09 17:14 17:19 17:24 17:29 17:33 17:39 17:44 17:49 17:54 17:59 18:04 33
Hemodynamic Results PRE POST PA Pressure: 57/23/35 35/20/25 PA Sat: 25% 63% 34
35
Conclusions • Pulmonary embolism remains a complex disease state • Multiple options exist for treatment • Considerations for choice of therapy should include: • Patient clinical status (signs of RV strain and hemodynamic compromise) • Thrombus burden/location • Bleeding risk • Goals of therapy • Access to technology and catheter skill sets • I predict strong growth in catheter-based intervention for PE due to improving technologies and results of ongoing research
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