TATORTNSTEMI A prospective randomized trial of Thrombus Aspiration

TATORT-NSTEMI: A prospective, randomized trial of Thrombus Aspiration in Thr. Ombus containing cul. Pri. T lesions in Non-ST-Segment Elevation Myocardial Infarction Holger Thiele, MD Ingo Eitel, MD; Suzanne de Waha, MD; Steffen Desch, MD; Bruno Scheller, MD; Bernward Lauer, MD; Meinrad Gawaz, MD; Tobias Geisler, MD; Oliver Gunkel, MD; Leonhard Bruch, MD; Norbert Klein, MD; Dietrich Pfeiffer, MD; Gerhard Schuler, MD; Uwe Zeymer, MD on behalf of the TATORT-NSTEMI Investigators

Disclosures Funding: Unrestricted grants by Terumo Europe, Leuven, Belgium Lilly Germany, Bad Homburg, Germany Potential Conflict of Interest: Research Funding: Terumo, Lilly, Medicines Company, Maquet Cardiovascular, Teleflex Medical Speaker Honoraria: Lilly, Astra Zeneca, Daiichi Sankyo, Boehringer Ingelheim, Maquet Cardiovascular, Medicines Company

Background 2008 Thrombectomy Guidelines STEMI I IIa IIb III 2010 2012 I IIa IIb III ESC 2009 2013 I IIa IIb III ACC/AHA NSTEMI Might be considered, no data! Hamm et al. Eur Heart J 2011; 32: 2999 -3054 O‘Gara et al. Circulation 2013; 127: e 362 -e 425 Steg et al. Eur Heart J 2012; 33: 2569– 2619 Kushner et al. JACC 2009; 54; 2205 -2241 Wijns et al Eur Heart J 2010; 31: 2501 -2555 Van de Werf et al. Eur Heart J 2008; 29, 2909– 2945

Methods Inclusion Criteria NSTEMI with 1. Ischemic symptoms > 20 minutes 2. Last symptoms within 72 h pre randomization 3. Elevated cardiac troponin T or I above 99. percentile 4. Identifiable culprit lesion with relevant thrombus (TIMI thrombus-grade 2 -5 in lesion) with intended PCI Grade Thrombus Description 0 No Thrombus No angiographic characteristics for thrombus 1 Possible thrombus Angiography demonstrates thrombus characteristics such as reduced contrast density, haziness, irregular lesion contour or a smooth convex (meniscus) at the site of total occlusion suggestive but not diagnostic of thrombus 2 Thrombus present (small size) Definitive thrombus with greatest dimension ≤ ½ vessel diameter 3 Thrombus present (medium size) Definitive thrombus with greatest dimensions > ½ vessel diameter but < 2 vessel diameter 4 Thrombus present (large size) Definitive thrombus with greatest dimension > 2 vessel diameter 5 Total occlusion

Methods Study Endpoints Primary Study Endpoint: Microvascular obstruction day 1 -4 in CMR Secondary Study Endpoints: § Infarct size measured by delayed enhancement CMR day 1 -4 § “Myocardial salvage” by CMR § Combined clinical endpoint: Mortality, reinfarction, TVR, and congestive heart failure 6 months after randomization § Individual clinical endpoints of combined endpoint § TIMI-flow post PCI § Myocardial blush grade post PCI § Enzymatic infarct size measured by Troponin T at 24 and 48 h de Waha et al. Trials. 2013; 14: 110

Background Late Microvascular Obstruction + Mortality Extent late MO 100 80 80 60 p=0. 01 40 20 0 0 No MO MO 40 10 30 20 Time to event (months) Survival (%) Presence late MO 60 p=0. 001 40 Tertile 1 Tertile 2 Tertile 3 0 40 10 30 0 20 Time to event (months) 20 de Waha et al. Eur Heart J 2010; 31: 2660 -2668

Methods CMR Protocol Contrast. Injection 1, 5 mmol/kg/BW Bolus Gd i. v. 0 5 Function 4 CH + 2 CH 10 T 2 SA 15 20 25 Function SA 30 35 Delayed enhancement 4 CH + 2 CH + SA 40 Time (min) Survey Area at risk EF, EDV, ESV Late MO + infarct size de Waha et al. Trials. 2013; 14: 110

Methods Study Design, Flow, and Compliance 460 NSTEMI patients 20 not randomized 440 NSTEMI patients 221 assigned to thrombectomy No CMR (n=40) Claustrophobia (n=11) PM/ICD (n=2) Obesity (n=1) Death (n=3) Renal insuff. (n=0) Other (n=23) Primary endpoint analysis MO (n=181) Secondary endpoint MBG (n=221) Secondary endpoint TIMI-flow (n=221) Clinical follow-up 6 months (n=218) No CMR (n=27) Claustrophobia (n=5) PC/ICD (n=3) Obesity (n=1) Death (n=3) Renal insuff. (n=1) Others (n=14) Primary endpoint analysis MO (n=192) Secondary endpoint MBG (n=219) Secondary endpoint TIMI-flow (n=219) Clinical follow-up 6 months (n=216)

Results Primary Study Endpoint - MO Presence of MO Extent of MO 10 p=0. 74 30. 8% 29. 2% Extent of MO, %LV Presence MO, % 8 Median [IQR] 1. 95% [0. 80; 4. 10] Median [IQR] 1. 40% [0. 70; 2. 60] p=0. 17 6 4 2 Thrombectomy Standard PCI Core lab assessed 0 Thrombectomy Standard PCI

Results MO – Predefined Subgroups Baseline variable Mean Difference in MO %LV (95% CI) P-value for interaction All Patients 0. 78 Male sex Female sex 0. 83 0. 76 Diabetes No diabetes 0. 92 0. 70 TIMI thrombus grade 2 -4 TIMI thrombus grade 5 0. 97 0. 64 TIMI-flow pre PCI 0 -1 TIMI-flow pre PCI 2 -3 0. 73 0. 91 Glycoprotein IIb/IIIa-inhibitor No glycoprotein IIb/IIIa-inhibitor 0. 20 0. 46 3 2 1 Thrombectomy better 0 -1 -2 -3 Standard PCI better

Results Myocardial Blush Grade p=0. 63 62. 6% % 0 1 2 Core lab assessed 3 0 1 2 Myocardial Blush Grade 3

Results Cumulative incidence of death, reinfarction, TVR, and new congestive heart failure (%) Clinical Outcome 6 Months 100 Thrombectomy 90 Standard PCI p=0. 20; log-rank test 80 0 50 100 Time after randomization (days) 150

Summary + Conclusions • In this first randomized, multicenter trial in patients with NSTEMI with thrombus containing lesions aspiration thrombectomy led to aspiration of thrombus material in 74%. • This led to a higher rate of primary stent implantation in comparison to standard PCI. • However, aspiration thrombectomy did not reduce the extent of microvascular obstruction in comparison to standard PCI without thrombectomy. • The results are also supported by a lack of benefit in secondary endpoints.

Acknowledgement TATORT-NSTEMI Investigators from 7 sites in Germany Steering Committee Angio Core Lab Homburg H. Thiele (Chair) B. Scheller U. Zeymer B. Scheller (Chair) T. Dani CMR Core Lab Leipzig Sponsors Lilly Germany Terumo Europe I. Eitel (Coordinator) T. Arndt CEC S. Desch (Chair) H. Thiele CRO at Institut für Herzinfarktforschung S. Avsar (Chair) M. Horack M. Neumer Study Sites Leipzig – Heart Center: H. Thiele Leipzig – University: N. Klein, D. Pfeiffer Berlin: L. Bruch Frankfurt (Oder): O. Gunkel Tübingen: T. Geisler, M. Gawaz Ludwigshafen: U. Zeymer Bad Berka: B. Lauer