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 AstraZeneca 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 thromboemboli Distal embolization occurred in 15% patients after primary PCI  ↓ ST resolution ↑ Infarct size ↑ Mortality What is the impact of macroscopic dital embolization. Distal embolization is related to reduced myocardial reperfusion, more extensive myocardial damage and a poor prognosis. Therefore, additional pharmacological interventions and mechanical devices should be studied to prevent and treat distal embolization. Henriques JPS et al. EHJ 2002;23:1112-7

Macroscopic embolic debris is retrieved in >75% of primary PCI cases How common is distal embolization: macroscopic embolic debris as you can see in these patients is retrieved in more that 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 These are results from three trials assessing infarct size in thrombus aspiration vs. Controls. P=0.004 P=0.20 P=0.46 Rescue catheter Export 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 5

INFUSE-AMI - Primary powered endpoint - Median [IQR] 17.0% [9.0, 22.8] Median [IQR] 17.3% [7.1, 25.5] P=0.51 N=452 All anterior MI Sx-hosp <4 hrs TIMI 0-2 Infarct size, %LV Aspiration N=229 No aspiration N=223 Stone GW et al. JAMA 2012;307:1817-26

TAPAS: 1,071 pts 30 days 4.0% vs. 2.1% P=0.07 Time (days) Mortality (%) Conventional PCI Thrombus-Aspiration 100 200 300 400 2 4 6 8 10 12 1 year 7.6% vs. 4.0% P=0.04 A large confirmatory trial is needed (small trials with unexpected large effect sizes, need to be replicated) Vlaar et al. Lancet 2008;371:1915-20

All-cause mortality 1,071 pts 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

Reinfarction Stent thrombosis TASTE, N= 7.244 2.7 HR 1 year 0.97 (0.73 – 1.28), P=0.81 HR 1 year 0.84 (0.50 – 1.40), P=0.51 HR 30 days 0.61 (0.34 - 1.07), P=0.09 HR 30 days 0.47 (0.20 - 1.02), P=0.06 N Engl J Med. 2013 Oct 24;369(17):1587-97 N Engl J Med. 2014 Sep 18;371(12):1111-20

All-cause mortality at 1 year Results consistent across major subgroups. 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 1er Endpoint: risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days Patients with STEMI were assigned to primary PCI with or without thrombectomy 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 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

Johnson, Vizzi, Strange Baumbach Residual thrombus burden Johnson, Vizzi, Strange Baumbach EuroIntervention 2014;10:167-168

Bhindi et al European Heart Journal (2015) 36, 1892–1900 TOTAL OCT-substudy Culprit lesion thrombus burden after thrombus aspiration Pre-stent Post-stent Bhindi et al European Heart Journal (2015) 36, 1892–1900

Distal Embolization During Primary PCI DE occurred in 30/450 pts (6.7%) after primary PCI with thrombus aspiration, and in 26/433 pts (6.0%) after primary PCI w/o aspiration Timing of first embolization Present on initial angiogram After guidewire passage After aspiration or balloon After stent Fokkema M et al. Eur Heart J. 2009;30:908-15

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