on behalf of the TOTAL Investigators 1 year results of the TOTAL trial: Randomized trial of manual Thrombectomy in STEMI SS Jolly, JA Cairns, S Yusuf, MJ Rokoss, P Gao, B Meeks, S Kedev, G Stankovic, R Moreno, A Gershlick, S Chowdhary, S Lavi, K Niemelä, I Bernat, WJ Cantor, AN Cheema, PG Steg, RC Welsh, T Sheth, OF Bertrand, A Avezum, R Bhindi, MK Natarajan, D Horak, RCM Leung, S Kassam, SV Rao, M El-Omar, SR Mehta, JL Velianou, S Pancholy, V Džavík on behalf of the TOTAL Investigators

Disclosures TOTAL trial was funded by: Canadian Institutes of Health Research Canadian Network and Centre for Trials Internationally (CANNeCTIN) Medtronic Inc.

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

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 PCI Alone (only bailout thrombectomy) Primary Outcome: CV death, MI, cardiogenic shock and class IV heart failure ≤180 days Safety Outcome: Stroke ≤30 days 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

Summary of Primary Results of TOTAL trial Improvement in Surrogate Outcomes (ST resolution, Distal embolization) Thrombectomy did not reduce primary outcome at 180 days Increase in stroke at 30 days Question: Would the benefit for surrogate outcomes translate into a long term benefit at 1 year? Jolly SS, et al. N Engl J Med. 2015;372:1389-1398.

Primary Outcome at 1 year Thrombectomy (N=5033) (%) PCI alone (N=5030) (%) HR 95% CI p CV death, MI, shock or class IV heart failure 395 (7.8) 394 (7.8) 1.00 (0.87 – 1.15) 0.99 CV death 179 (3.6) 192 (3.8) 0.93 (0.76 – 1.14) 0.48 Recurrent MI 125 (2.5) 118 (2.3) 1.05 (0.82 -1.36) 0.68 Cardiogenic Shock 95 (1.9) 105 (2.1) 0.90 (0.68 – 1.19) 0.47 Class IV heart failure 106 (2.1) 96 (1.9) 1.01 (0.83 – 1.45) 0.50

Safety Outcomes at 1 year   Thrombectomy (N=5033) (%) PCI alone (N=5030) (%) HR 95% CI p Stroke at 1 year 60 (1.2) 36 (0.7) 1.66 (1.10 – 2.51) 0.015 Stroke or TIA at 1 year 73 (1.4) 44 (0.9) 1.65 (1.14 – 2.40) 0.008 Landmark Analyses Stroke 180 days to 1 year 7 (0.1) 10 (0.2) 0.70 (0.27 – 1.83) 0.46

Updated Meta-analysis N=20,352 All-Cause Mortality OR 0.90 (95% CI 0.79-1.02) P=0.10

Stroke 0.9% thrombectomy vs. 0.6% PCI alone, OR 1.43 (95% CI 1.03-1.99) P=0.03

Conclusions Routine thrombectomy compared to PCI alone did not reduce CV death, MI, shock or heart failure at 1 year Routine thrombectomy was associated with increased rate of stroke Manual Thrombectomy can no longer be recommended as a routine strategy

Available Online at the Lancet