Is There Still a role for Thrombus Aspiration

Is There Still a role for Thrombus Aspiration in STEMI? Sanjit Jolly MD MSc, FRCP(C) Associate Professor, Interventional Cardiologist Populaltion Health Research Institute, Mc. Master University Hamilton, Canada TOTA L

Disclosures • Grant Support from Medtronic • Speakers fees from Medtronic, Astra Zeneca TOTA L

Case 1 • 52 yo male with inferior STEMI • Prior stent to LCX 1 month prior • Received 600 mg clopidogrel, Aspirin, IV UFH TOTA L

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What Next • GP IIb IIIa inhibitors • Manual Thrombectomy • Intracoronary imaging TOTA L

Thrombus brought back to Left Main TOTA L

Case • Patient deteriorates with widespread ST depression, hypotension • More thrombectomy ineffective • Guide catheter fails to aspirate clot • Clot pushed back into LCx and broken up with a balloon • More evidence needed for routine thrombectomy TOTA L

Case 2 • 54 yo male, prolonged CP, ST elevation AVR , diffuse ST depression. Cardiogenic shock TOTA L

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After PTCA 2. 5 x 15 TOTA L

Case • Patient detiorating requiring high dose Norepinephrine • Intubated • Thrombectomy TOTA L

Post Thrombectomy TOTA L

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Epicardial flow is important However, 94% of patients achieve TIMI 3 flow following primary PCI TOTA L Stone GW, et al. JACC 2002; 39: 591 -7.

Microvascular dysfunction in patients with normal epicardial flow TOTA L • 29% of patients with TIMI 3 flow have microvascular dysfunction Stone GW, et al. JACC 2002; 39: 591 -7. (Myocardial blush grade <3)

Rationale for Thrombectomy Major Limitation of Primary PCI: Distal Embolization and Reduced Flow TOTA L Hypothesis: Aspiration thrombectomy may reduce embolization and improve clinical outcomes

TAPAS trial Single center trial of Thrombectomy vs. PCI alone during PPCI (N=1071) Primary Outcome: Surrogate Cardiac Mortality P<0. 001 Trend at 30 days became significant at 1 year TOTA L Svilaas T, et al. N Engl J Med. 2008; 358: 557 -67. Vlaar PJ, 20 et al. Lancet 2008; 371: 1915 -20.

Guidelines Changed after TAPAS • Routine Manual Thrombectomy Class IIa recommendation ACC/AHA & ESC • Thrombectomy use marked increased • 20% use in STEMI in USA, 30 -40% in STEMI in Europe TOTA L

TOTA L Jolly SS, et al. N Engl J Med. 2015; 372: 1389 -98.

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 • TOTA L 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

PCI Variables and Surrogate Outcomes Thrombectomy PCI alone N=5033 N=5030 PCI Procedure time (median) 39 min 35 min <0. 001 Direct Stenting 38. 3% 21. 3% <0. 001 Final TIMI 3 flow* 93. 1% 0. 12 Distal Embolization* 1. 6% 3. 0% <0. 001 ST segment Resolution <70%* 27. 0% 30. 2% <0. 001 P * Investigator Reported Outcomes. Core laboratory analysis is ongoing. TOTA L Jolly SS, et al. N Engl J Med. 2015; 372: 1389 -98.

Primary Outcome Day 180 Thrombectomy PCI alone HR 95% CI p 351 (7. 0%) 0. 99 0. 85 -1. 15 0. 86 157 (3. 1%) 174 (3. 5%) 0. 90 0. 73 -1. 12 0. 34 Recurrent MI 99 (2. 0%) 92 (1. 8%) 1. 07 0. 81 -1. 43 0. 62 Cardiogenic Shock 92 (1. 8%) 100 (2. 0%) 0. 92 0. 69 -1. 22 0. 56 Class IV heart failure 98 (1. 9%) 90 (1. 8%) 1. 09 0. 82 -1. 45 0. 57 (N=5033) (%) (N=5030) (%) CV death, MI, shock or class IV heart failure 347 (6. 9%) CV death TOTA L Jolly SS, et al. N Engl J Med. 2015; 372: 1389 -98.

Safety Outcomes Thrombectomy PCI alone HR 95% CI p 16 (0. 3%) 2. 06 1. 13 -3. 75 0. 015 42 (0. 8%) 19 (0. 4%) 2. 21 1. 29 -3. 80 0. 003 52 (1. 0%) 25 (0. 5%) 2. 08 1. 29 -3. 35 0. 002 (N=5033) (%) (N=5030) (%) Stroke within 30 days 33 (0. 7%) Stroke or TIA within 30 days Stroke within 180 days TOTA L

Subgroup Analysis Primary Outcome Thrombectomy PCI Alone OVERALL TIMI Thrombus Grade: ≥ 3 <3 10063 (%) 6. 9 (%) 7. 0 9052 998 7. 0 5. 2 7. 3 3. 9 0. 264 7943 2107 7. 3 5. 3 7. 5 4. 8 0. 516 8375 1665 6. 6 8. 1 6. 6 8. 8 0. 660 7443 2519 7. 4 5. 6 7. 8 4. 7 0. 219 2450 2139 5474 7. 3 7. 2 6. 6 7. 9 6. 5 6. 7 0. 659 4016 6037 9. 0 5. 6 9. 2 5. 5 0. 774 6662 3401 4. 7 11. 4 4. 3 12. 1 0. 360 P (INTERACTION) TIMI Thrombus Grade: ≥ 4 <4 Symptom Onset: <6 hrs 6 -12 hrs Initial TIMI Flow: 0 -1 2 -3 Site Primary PCI Volume: Tertile 1 Tertile 2 Tertile 3 MI Type: Anterior Non-Anterior Age: ≤ 65 yrs >65 yrs TOTA L 0. 5 Favours Thrombectomy 1. 0 2. 0 Favours PCI Alone

Mortality of Stroke within 180 days Hazard ratio, 10. 17 (95%CI, 6. 70 -15. 45); P<0. 0001) 0. 35 30. 8% Cumulative % of Death 0. 30 0. 25 0. 20 With Stroke 0. 15 0. 10 0. 05 3. 4% Without Stroke 0 0 1 2 No. at Risk TOTA L 3 4 5 6 Months of Follow-up With Stroke 78 62 58 56 54 54 53 Without Stroke 9985 9713 9658 9630 9614 9597 9570

Meta-Analysis for Stroke 0. 8% Thrombectomy vs. 0. 5% PCI alone, OR 1. 59; 95% CI 1. 11 -2. 27, p=0. 01 TOTA L Jolly SS, et al. Eur Heart J. 2015; online

OCT Substudy of TOTAL • No difference in thrombus volume between Thrombectomy and PCI alone group • Overall Thrombus volume lower than expected • IMPLICATION: NOT a failure of manual thrombectomy to remove thrombus TOTA L Bhindi R, et al. Eur Heart J. 2015; Online.

Summary • Routine thrombectomy was associated with increased risk of stroke that was evident within 48 hours • Thrombectomy should be used as a bailout therapy after balloon inflation (TOTAL bailout criteria) • High thrombus burden with reduced flow • Persistent Thrombus after stent deployment TOTA L