Thrombus Management in the Cath Lab David A

Thrombus Management in the Cath Lab  David A. Cox, MD FSCAI FACC Lehigh Valley Health Network Director, Cardiovascular Research Institute Associate Director of Cardiac Catheterization Laboratory Allentown, PA CRT 2016

Disclosures • Advisory Board: Abbott Vascular Medtronic, Inc. the. Medicines. Company

We All Agree • Dealing with thrombus still a real challenge • “Why are trials negative? I did thrombectomy and it works!” • Doctor feels good, any benefit for patient?

What PCI doc’s already know • Is the size and amount of thrombus really that important? • YES!

MACE Importance of Thrombus Burden MACE after DES for STEMI MACE (death, MI, TVR) p < 0. 001 Large Thrombus Burden 24. 9% 15. 3% 1 Small Thrombus Burden Months Sianos JACC 2007

Lots of papers in this area

Embolic Protection During Primary PCI: Impact of single vs. multicenter studies 25 RCTs, 5919 pts 2460 pts in single center trials, 3459 pts in multicenter trials Predictors of mortality Study design Single center Multicenter Overall (I 2=0, P=0. 51) 2 Predictors of ST resolution RR (95%) 0. 58 (0. 37, 0. 90) 1. 01 (0. 67, 1. 54) 0. 81 (0. 72, 0. 91) 1 4 Study design Single center Multicenter Overall (I 2=84. 8%, p<0. 001) 0. 3 RR (95%) 0. 58 (0. 37, 0. 90) 1. 01 (0. 67, 1. 54) 0. 75 (0. 72, 0. 79) 1 Inaba Yet al. Eurointervention; 2009; 5: 375 -83 2

Filters…no data for use

Some exceptions Massive thrombus in proximal vessel……. Run manual thrombectomy device over filter placed distally. OR Some reports of literally catching the clot with the filter as a butterfly net!!! DATA-FREE ZONE!

What’s new in embolic protection?

MGuard Concept STENT + EMBOLIC PROTECTION

The MGuard and MGuard Prime Embolic Protection Stent (EPS) MGuard Metallic frame 316 L stainless steel Strut width 100 µm Crossing profile 1. 1 – 1. 3 mm Shaft dimensions 0. 65 – 0. 86 mm Mesh sleeve PET** - Fiber width 20 µm - Net aperture size 150 - 180 µm MGuard Prime L 605 cobalt chromium 80 µm 1. 0 – 1. 2 mm 0. 65 – 0. 86 mm PET** 20 µm 150 - 180 µm *Inspire. MD, Tel Aviv, Israel; **Polyethyleneterephthalate

Primary Endpoint: Master I Complete ST-segment resolution MGuard (n=204) 16. 7% 25. 5% Control (n=206) 17. 0% 44. 7% 57. 8% 38. 3% Difference [95%CI] = 13. 2% [3. 1, 23. 3] Stone GW et al. J Am Coll Cardiol 2012; 60: 1975– 84 P=0. 008

MASTER II Primary Endpoint Complete ST-segment resolution MGuard Prime (n=144) 10. 4% 32. 6% Control (n=145) 11. 0% 56. 9% 29. 7% 59. 3% Difference [95%CI] = -2. 4% [-14. 5, 9. 7] P=0. 68

Manual Thrombectomy

TAPAS: 1, 071 pts with STEMI undergoing PCI randomized in the ER to aspiration (Export) vs. control Myocardial Blush (1 EP) ST-segment Resolution P<0. 001 Thrombus aspiration Conventional PCI P<0. 001 Thrombus aspiration Svilaas T et al. NEJM 2008; 358; -557 -67 Conventional PCI

TAPAS: 1, 071 pts with STEMI undergoing primary PCI randomized in the ER to manual aspiration (Export) vs. control 12 30 days 4. 0% vs. 2. 1% P=0. 07 10 Mortality (%) Conventional PCI Thrombus-Aspiration 1 year 7. 6% vs. 4. 0% P=0. 04 8 6 4 2 0 0 100 200 300 Time (days) Vlaar et al. Lancet 2008; 371: 1915 -20 400

Why might manual aspiration work? • Easy to use • Can chase clot down artery • Direct Stenting? • Thrombectomy: remove clot, size appropriately, and direct stent with no post-dilatation…. may all lead to less no -reflow, better STR, etc

UCR Uppsala Clinical Research Center Thrombus Aspiration in ST- Elevation myocardial infarction in Scandinavia (TASTE trial): Results and Methodology of a Registry based Randomized Clinical Trial (RRCT) Ole Fröbert, MD, Ph. D - on behalf of the TASTE investigators Departement of Cardiology Örebro University Hospital Sweden

TASTE and previous studies TASTE TAPAS JETSTENT AIMI INFUSE-AMI VAMPIRE PREPARE Chevalier Kaltoft MUSTELA X AMINE ST PIHRATE EXPIRA DEAR-MI Liistro 0 1000 2000 3000 4000 Number of patients 5000 6000 7000 8000

All-cause mortality at 30 days HR 0. 94 (0. 72 - 1. 22), P=0. 63 Per protocol analysis based on actual treatment: HR 0. 88 (0. 66 - 1. 17), P=0. 38 Fröbert, O. et al. N Engl J Med 2013; 369: 1587 -97

Additional results

TASTE vs. TAPAS

TASTE 12 mo: NO BENEFIT

The TOTAL Trial Study Design STEMI* with Primary PCI ≤ 12 hours of symptom onset Sample size of 10, 700 for 80% power to detect a 20% Relative Risk Reduction 1: 1 Randomization between strategies Routine Upfront Manual Thrombectomy followed by PCI Alone (only bailout thrombectomy) Primary Outcome: CV death, MI, cardiogenic shock and class IV heart failure ≤ 180 days Safety Outcome: Stroke ≤ 30 days • TO TA Bailout Thrombectomy allowed if PCI alone strategy fails: Persistent TIMI 0 or 1 flow with large thrombus after balloon pre-dilatation • Persistent large thrombus after stent deployment at target lesion

Summary of Primary Results of TOTAL trial • Improvement in Surrogate Outcomes (ST resolution, Distal embolization) • Thrombectomy did not reduce primary outcome at 180 days • Increase in stroke at 30 days Question: • Would the benefit for surrogate outcomes translate into a long term benefit at 1 year? TO TA Jolly SS, et al. N Engl J Med. 2015; 372: 1389 -1398.

Primary Outcome at 1 year Thrombecto my (N=5033) (%) PCI alone (N=5030) (%) HR 95% CI p CV death, MI, shock or class IV heart failure 395 (7. 8) 394 (7. 8) 1. 00 (0. 87 – 1. 15) 0. 99 CV death 179 (3. 6) 192 (3. 8) 0. 93 (0. 76 – 1. 14) 0. 48 Recurrent MI 125 (2. 5) 118 (2. 3) 1. 05 (0. 82 -1. 36) 0. 68 Cardiogenic Shock 95 (1. 9) 105 (2. 1) 0. 90 (0. 68 – 1. 19) 0. 47 Class IV heart failure 106 (2. 1) 96 (1. 9) 1. 01 (0. 83 – 1. 45) 0. 50 TO TA

Safety Outcomes at 1 year Thrombectom y (N=5033) (%) PCI alone (N=5030) (%) HR Stroke at 1 year 60 (1. 2) 36 (0. 7) 1. 66 Stroke or TIA at 1 year 73 (1. 4) 44 (0. 9) 1. 65 7 (0. 1) 10 (0. 2) 0. 70 Landmark Analyses Stroke 180 days to 1 year TO TA 95% CI (1. 10 – 2. 51) (1. 14 – 2. 40) (0. 27 – 1. 83) p 0. 015 0. 008 0. 46

Conclusions • Routine thrombectomy compared to PCI alone did not reduce CV death, MI, shock or heart failure at 1 year • Routine thrombectomy was associated with increased rate of stroke • Manual Thrombectomy can no longer be recommended as a routine strategy TO TA

TATORT-NSTEMI: A prospective, randomized trial of Thrombus Aspiration in Thr. Ombus containing cul. Pri. T lesions in Non-ST-Segment Elevation Myocardial Infarction Holger Thiele, MD Ingo Eitel, MD; Suzanne de Waha, MD; Steffen Desch, MD; Bruno Scheller, MD; Bernward Lauer, MD; Meinrad Gawaz, MD; Tobias Geisler, MD; Oliver Gunkel, MD; Leonhard Bruch, MD; Norbert Klein, MD; Dietrich Pfeiffer, MD; Gerhard Schuler, MD; Uwe Zeymer, MD on behalf of the TATORT-NSTEMI Investigators

Effect of Thrombus Aspiration in Patients With Myocardial Infarction Presenting Late After Symptom Onset Steffen Desch, MD Thomas Stiermaier, MD; Suzanne de Waha, MD; Philipp Lurz, MD, Ph. D; Matthias Gutberlet, MD; Marcus Sandri, MD; Norman Mangner, MD; Enno Boudriot, MD; Michael Woinke, MD; Sandra Erbs, MD; Gerhard Schuler, MD; Georg Fuernau, MD; Ingo Eitel, MD; Holger Thiele, MD

Should we stop thrombectomy? • • • Oculothrombotic reflex Allows direct stenting May reduce distal embolization/no-reflow Techniques in trials poorly defined Selective thrombectomy with PPCI 2 b per Oct 2015 STEMI GDLS J Blankenship JACC Int Jan 2016: Why we will never stop aspirating coronary thrombi

IMPACT TRIAL • CRT 2016 • SCAAR STEMI Patient Registry • Positive for stent thrombosis

With effective pharmacotherapy, should primary PCI be deferred? A randomised Trial of Deferred vs. Immediate Stenting to Prevent No-reflow in Acute STEMI Berry C, Carrick D, Mc. Entegart M, Haig C, Petrie M, Eteiba H, Hood S, Owens C, Watkins S, Layland J, Behan M, Sood A, Hillis W, Mordi I, Mahrous, A, Ahmed N, Wilson R, Lasalle L, Lindsay MML, Peat E, Rae A, Généreux P, Ford I, Oldroyd KG. University of Glasgow, Golden Jubilee National Hospital, UK; Cardiovascular Research Foundation and Columbia University Medical Center, New York.

All comers – STEMIs assessed for eligibility N = 411 (March – Nov 2012) TIMI 3 flow asp thrombectomy+/POBA Enrollment Randomized n=101 Deferred stenting Usual care Immediate PCI, n = 49 4 - 16 hrs later, n = 52 Heparin, gp. IIb. IIIa, enoxaparin 1 mg/kg CCU

Results Immediate stenting Deferred stenting p = 0. 006 p = 0. 008 33 29 p = 0. 054 14 10 6 2

CHAMPION PHOENIX Overall and STEMI outcomes, 48 h Primary Endpoint Cangrelor Clopidogrel OR Overall m. ITT (N=10, 942) 257/5470 (4. 7%) 322/5469 (5. 9%) 0. 78 (0. 66 -0. 93) STEMI (n=1, 991) 27/961 (2. 8%) 38/1030 (3. 7%) 0. 75 (0. 46 -1. 25) Overall m. ITT (N=10, 942) 46/5470 (0. 8%) 74/5469 (1. 4%) 0. 62 (0. 43 -0. 90) STEMI (n=1, 991) 12/961 (1. 2%) 20/1030 (1. 9%) 0. 64 (0. 31 -1. 31) Overall safety (N=11, 056) 31/5529 (0. 6%) 19/5527 (0. 3%) 1. 63 (0. 92 -2. 90) STEMI (n=2, 070) 12/1000 (1. 2%) 7/1070 (0. 7%) 1. 84 (0. 72 -4. 70) Stent Thrombosis GUSTO sev/mod bleeding Bhatt DL, Stone GW, Mahaffey KW, et al…. Harrington RA. NEJM 2013; 68: 1303 -13 and online appendix.

IPST in CHAMPION PHOENIX Phoenix 10, 939 pts assessed by a blinded core lab Frequency of IPST (n=89) P=0. 0006 89/10, 939 32/6138 33/2810 Genereux et al. J Am Coll Cardiol 2014; 63: 619– 29 24/1991

IPST in CHAMPION PHOENIX 10, 939 pts assessed by a blinded core lab Phoenix Impact on 30 -day mortality IPST No IPST Mortality (%) 10. 1% HR [95%CI] = 11. 04 [5. 59 , 21. 79] P <0. 0001 1. 0% Days from Randomization No at risk: IPST: No IPST: 89 10850 84 10781 82 10759 80 10741 80 10735 Genereux et al. J Am Coll Cardiol 2014; 63: 619– 29 80 10727 79 10688

IPST in CHAMPION PHOENIX 10, 939 pts assessed by a blinded core lab Phoenix Reduction of IPST with cangrelor IPST (%) P Int = 0. 77 OR 0. 65 [0. 42, 0. 99] p=0. 04 OR 0. 75 [0. 38, 1. 50] p=0. 42 OR 0. 50 [0. 24, 1. 05] p=0. 06 Généreux P et al. JACC 2013. OR 0. 76 [0. 34, 1. 73] p=0. 52

Which Intraprocedural Thrombotic Events Impact Clinical Outcomes After Percutaneous Coronary Intervention in Acute Coronary Syndromes? A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials Jeffrey D. Wessler, MD, MPH; Philippe Généreux, MD; Roxana Mehran, MD; Girma Minalu Ayele, Ph. D; Sorin J. Brener, MD; Margaret Mc. Entegart, MD, Ph. D; Ori Ben. Yehuda, MD; Gregg W. Stone, MD; Ajay J. Kirtane, MD, SM J Am Coll Cardiol Intv. 2016; 9(4): 331 -337

Results • 6591 pts PCI for NSTEMI or STEMI • IPTE 7. 7% • 12/2% STE 3. 5% NSTEMI

Conclusions: 2016 IC Abciximab No benefit via guide Clearway-catheter: small infarct size reduction. . enough to justify cost? Aspiration thrombectomy No data in well-powered multicenter trials that thrombectomy reduces clinical endpts.

Conclusions: Thrombus 2016 • Aspiration: selective • Flow may be the best treatment for clot…are we back to simply getting placing a stent with appropriate pharmacology?