Rationale for TOTAL trial randomized trial of routine

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

Disclosures Received Grant Support from Medtronic Received Speakers honoria from Glaxo. Smith. Kline, Sanofi-Aventis, Astra Zeneca, Boehringer Ingelheim

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

Microvascular dysfunction in patients with normal epicardial flow • 29% 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.

Review of three largest trials of Thrombectomy

AIMI Trial: Mechanical Thrombectomy increased infarct size and mortality P=0. 03 Ali, A, et al. JACC. 2006; 48: 244 -. 252.

TAPAS trial : Benefit for Surrogate outcome Single 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: 557 -67.

Unexpected Reduction in Mortality at 1 year Trend 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)

JET STENT: No difference in Infarct Size, mortality with mechanical thrombectomy P=0. 40 P=ns Migliorini, A, et al. JACC. 2010; 56: 1298.

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

Stroke: Risk of Harm Trend toward increased risk of stroke with devices 1. 9% vs. 0. 3% RR 3. 43 (95% CI 0. 85 -13. 9), p=0. 085 Emphasizes the need for a definitive multicenter trial Bavry et al. Eur Heart J. 2008. 29; 2989 -3001.

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

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

International STEMI survey 27 item online survey (Survey Monkey. TM) 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. 2010. AHA abstract

Routine Use of Aspiration thrombectomy during PPCI • Only 36% use aspiration thrombectomy routinely with no significant variation by region

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

Need for a large RCT Existing evidence supports universal AT use A large, definitive AT trial is needed 89% agree 21% agree 85% perce nt responden of ts would randomize patient s

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

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

TOTAL trial Potential to be a landmark trial in STEMI Validate concept that thrombus removal improves clinical outcomes Lead to other breakthroughs in STEMI care If interested in partcipating contact email: total@phri. ca