Is the Debate Over Routine Thrombus Aspiration in

Is the Debate Over? Routine Thrombus Aspiration in STEMI (From TAPAS to INFUSE-AMI to TASTE to TOTAL) Stefan James Professor of Cardiology Uppsala Clinical Research Centre Uppsala University Uppsala, Sweden

Potential conflicts of interest • Astra. Zeneca Pharmaceuticals Institutional Research grants/ consultant/Honoraria • The Medicines Company Research grant/ consultant/ Honoraria • Jansen consultant/ Honoraria • Bayer consultant/ Honoraria • Thermo Fisher Consultant/ Honoraria • Swedish Research Council Research grant • Swedish Heart and Lung Foundation Research grant • Strategic Research Council Research grant

Impact of Macroscopic Distal Emboli Proximal LCX filling defect at primary PCI site Distal embolization occurred in 15% patients after primary PCI ↓ ST resolution ↑ Infarct size ↑ Mortality Distal thromboemboli Henriques JPS et al. EHJ 2002; 23: 1112 -7

Macroscopic embolic debris is retrieved in >75% of primary PCI cases The concept of thrombus aspiration prior to primary PCI in STEMI is intuitive and “feels right”

No evidence of reduction in Infarct Size P=0. 004 P=0. 20 P=0. 46 Rescue catheter Export catheter Kaltoft A et al. Circ 2006; 114: 40 -47 Sardella G et al. JACC 2009; 53: 309– 15 Svilaas T et al. NEJM 2008; 358; -557 -67

INFUSE-AMI - Primary powered endpoint Median [IQR] 17. 0% 17. 3% Infarct size, %LV [9. 0, 22. 8] [7. 1, 25. 5] P=0. 51 Aspiration N=229 Stone GW et al. JAMA 2012; 307: 1817 -26 No aspiration N=223 N=452 All anterior MI Sx-hosp <4 hrs TIMI 0 -2

TAPAS: 1, 071 pts 12 10 Mortality (%) Conventional PCI Thrombus-Aspiration 30 days 4. 0% vs. 2. 1% P=0. 07 1 year 7. 6% vs. 4. 0% P=0. 04 8 A large confirmatory trial is needed (small trials with 6 unexpected large effect sizes, need to be replicated) 4 2 0 0 100 200 Time (days) Vlaar et al. Lancet 2008; 371: 1915 -20 300 400

1, 071 pts All-cause mortality HR up to 1 year 0. 94 (0. 78 – 1. 15), P=0. 57 HR up to 30 days 0. 94 (0. 72 - 1. 22), P=0. 63 N Engl J Med. 2013 Oct 24; 369(17): 1587 -97 N Engl J Med. 2014 Sep 18; 371(12): 1111 -20

TASTE, N= 7. 244 Stent thrombosis Reinfarction 2. 7 HR 1 year 0. 97 (0. 73 – 1. 28), P=0. 81 HR 30 days 0. 61 (0. 34 - 1. 07), P=0. 09 N Engl J Med. 2013 Oct 24; 369(17): 1587 -97 N Engl J Med. 2014 Sep 18; 371(12): 1111 -20 HR 1 year 0. 84 (0. 50 – 1. 40), P=0. 51 HR 30 days 0. 47 (0. 20 - 1. 02), P=0. 06

All-cause mortality at 1 year N Engl J Med. 2013 Oct 24; 369(17): 1587 -97 N Engl J Med. 2014 Sep 18; 371(12): 1111 -20

TOTAL, N=10. 732 u Patients with STEMI were assigned to primary PCI with or without thrombectomy u At 180 days: there was no significant between-group difference in the primary outcome of death or cardiovascular events. N Engl J Med; Volume 372(15): 1389 -1398, 2015

TOTAL, N=10. 732 u Patients in the thrombectomy group had a higher rate of stroke at 30 days. N Engl J Med; Volume 372(15): 1389 -1398, 2015

TOTAL, N=10. 732

TASTE and TOTAL TASTE, N= 7. 244 TOTAL, N=10. 732 CV death, recurrent myocardial infarction, cardiogenic shock, or heart failure within 180 days

Residual thrombus burden Johnson, Vizzi, Strange Baumbach Euro. Intervention 2014; 10: 167 -168

TOTAL OCT-substudy Culprit lesion thrombus burden after thrombus aspiration 16 P=0. 24 14 12 10 8 Primary outcome P=0. 37 P=0. 33 6 P=0. 37 P=0. 14 4 P=0. 14 2 0 Thrombus burden Absolute thrombus volume Pre-stent max thrombus area Athero throbotic Absolute Max burden Atherothrombotic atherothrombotic burden area Post-stent Bhindi et al European Heart Journal (2015) 36, 1892– 1900

Conclusions The concept of thrombus aspiration prior to primary PCI in STEMI is intuitive and “feels right” Data from two major RCT 18000 patients show that routine aspiration does not reduce infarct size, MI, stent thrombosis, heart failure or mortality Routine thrombus aspiration is not beneficial in any investigated subgroup Thrombus aspiration is associated with an increased risk of stroke Routine aspiration should not be performed