1 Rationale for TOTAL trial: randomized trial of routine aspiration ThrOmbecTomy with PCI vs. PCI ALone in patients with STEMI undergoing primary PCI Sanjit Jolly MD MSc, FRCP(C) Assistant Professor, Interventional Cardiologist McMaster University Hamilton, Canada

2 Disclosures Received Grant Support from MedtronicReceived Speakers honoria from GlaxoSmithKline, Sanofi-Aventis,Astra Zeneca, Boehringer Ingelheim

3 Epicardial flow is importantHowever, 94% of patients achieve TIMI 3 flow after PPCI Stone GW, et al. JACC 2002;39:591-7.

4 Microvascular dysfunction in patients with normal epicardial flow29% of patients with TIMI 3 flow have reduced microvascular perfusion (Myocardial blush grade <3) after PPCI Stone GW, et al. JACC 2002;39:591-7.

5 Review of three largest trials of Thrombectomy

6 AIMI Trial: Mechanical Thrombectomy increased infarct size and mortalityP=0.03 Ali, A, et al. JACC.2006;48:

7 TAPAS trial : Benefit for Surrogate outcomeSingle center trial of Thrombectomy (Export) vs. PCI alone during PPCI (N=1071) Benefit for primary outcome of myocardial blush grade 0 or 1 (poor microvascular flow) P<0.001 Svilaas T, et al. N Engl J Med. 2008;358:

8 Unexpected Reduction in Mortality at 1 yearTrend at 30 days became significant at 1 year Experts cautioned that a large confirmatory trial is needed (small trials with unexpected large effect sizes, need to be replicated)

9 JET STENT: No difference in Infarct Size, mortality with mechanical thrombectomyP=0.40 P=ns Migliorini, A, et al. JACC. 2010;56:1298.

10 How do we explain conflicting results?Different thrombectomy devices have different clinical effects More likely: Small trials with few events unreliable A large scale definitive trial is needed

11 Stroke: Risk of Harm Trend toward increased risk of stroke with devices 1.9% vs. 0.3% RR 3.43 (95% CI ), p=0.085 Emphasizes the need for a definitive multicenter trial Bavry et al. Eur Heart J ;

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14 Paradigm Does removal of thrombus during PPCI improve clinical outcomes? Unanswered question: We have the opportunity to answer

15 Thrombectomy use only 4% of PPCI in USAData from ACC NDR registry of 217,355 primary PCI procedures

16 International STEMI survey27 item online survey (Survey MonkeyTM) Distributed to various investigator networks in North America, Europe and Asia and members of Canadian Association of Interventional Cardiology Received 477 responses (response rate 29%) Russo J, et al. Circulation AHA abstract

17 Routine Use of Aspiration thrombectomy during PPCIOnly 36% use aspiration thrombectomy routinely with no significant variation by region

18 Have you ever experienced a complications related to Aspiration Thrombectomy?1 in 5 interventionalists have experienced a serious complication related to thrombectomy

19 Existing evidence supports universal AT use Need for a large RCT Existing evidence supports universal AT use 21% agree A large, definitive AT trial is needed 85% percent of respondents would randomize patient s 89% agree

20 Summary Thrombectomy is not used routinely by majority of operators during PPCI TAPAS trial was promising but far from definitive Large multicenter randomized trial needed to determine benefits of routine thrombectomy on clinical outcomes

21 TOTAL Trial N=4000 Primary outcome: CV death, recurrent MI, cardiogenic shock and new or worsening NYHA Class IV HF at 180 days Contact Supported by Canadian Network and Center for Trials internationally and Medtronic

22 TOTAL trial Potential to be a landmark trial in STEMIValidate concept that thrombus removal improves clinical outcomes Lead to other breakthroughs in STEMI care If interested in partcipating contact