Trial Update- TOTAL. Jonathan Byrne

Transcription

1 Trial Update- TOTAL Jonathan Byrne

2 No conflicts of interest

3 Background- rationale for thrombectomy Major Limitation of primary PCI: distal embolisation and reduced flow Stonel JACC 2002;39:591-7 Henriques et al EHJ 2002;23:1112-7

4 Background-evidence Vlaar Lancet 2008;371: Positive effect of manual thrombectomy mainly driven by the TAPAS study Formed the basis of a Class IIa recommendation for routine thrombectomy in PPCI

5 TASTE >7000 patients included in TASTE Novel randomisation process using the SCAAR registry Concerns that lower risk population randomised Mortality in randomised cohort 2.6% vs >10% in the non-randomised Frobert NEJM 2013;369:

6 TOTAL- trial design Exclusions: Cardiogenic shock/fibrinolysis/prior CABG 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 large thrombus after pre-dilatation Primary outcome : CVwith death/mi/shock/class IV balloon heart failure Persistent large thrombus after stent deployment at target lesion

7 Recruitment North America 3863 Europe 5617 Asia Pacific 865 South America ,732 patients randomised from 87 sites

8 TOTAL Trial Flow and Adherence Exclusions: Cardiogenic shock/previous CABG/thrombolysed STEMI 10,732 enrolled and randomized 10,066 underwent PCI for STEMI randomized 5033 Manual Thrombectomy Crossover to PCI alone in 230 (4.6%) 5033 included in analysis 5030 PCI Alone Cross-over to Thrombectomy as initial strategy in 69 (1.4%) Bailout Thrombectomy in 355 (7.1%) 5030 included in analysis

9 Baseline Characteristics Thrombectomy PCI alone N=5033 N= years 61.0 years Male 76.8% 78.2% Killip Class 2 4.3% 4.2% Anterior MI 39.0% 40.9% Symptom onset to hospital arrival* 128 min 120 min Door to Device time 53.0 min 53.0 min Mean Age *P=0.024

10 PCI Procedural Details Pre PCI TIMI 0 flow Thrombectomy PCI alone N=5033 N= % 67.8% Final TIMI 3 flow* 93.1%90.8% 93.1% % Distal Embolization* Unfractionated Heparin 1.6% 80.8% 3.0% < % TIMI thrombus grade 3 ST segment Resolution Bivalirudin <70%* 18.7% 27.0% 30.2% 17.3% <0.001 Glycoprotein IIb/IIIa** 37.4% 41.4% Drug Eluting Stents 44.7% 45.0% Radial Access 68.3% 68.2% Higher rates of direct stenting in the thrombectomy arm and operator reported ST segment resolution/distal embolisation in thrombectomy arm

11 Outcome No difference in the primary outcome at 180 or 360 days (ITT, PP or as treated) No difference in rates of stent thrombosis, TVR Significantly higher rates of stroke in the thrombectomy arm (0.7% vs 0.3%) Difference apparent early (<48 hours), increase in ischaemic and haemorrhagic strokes rates maintained out to 180 days

12 Subgroup Analysis Primary Outcome Thrombectomy PCI Alone OVERALL TIMI Thrombus Grade: 3 < (%) 6.9 (%) P (INTERACTION) TIMI Thrombus Grade: 4 <4 Symptom Onset: <6 hrs 6-12 hrs Initial TIMI Flow: Site Primary PCI Volume: Tertile 1 Tertile 2 Tertile 3 MI Type: Anterior Non-Anterior Age: 65 yrs >65 yrs 0.5 Favours Thrombectomy Favours PCI Alone

13 Blush and embolisation? Angiographic sub-study included 1610 patients Blush grade similar between thrombectomy and PCI only, but distal embolisation without thrombectomy higher and associated with increased mortality

14 Thrombus burden/volume OCT substudy of 214 patients Patients well matched for baseline characteristics OCT performed pre-stent in both groups (after initial therapy) Thrombus burden was low in general (with no difference between groups). Bhindi EHJ 2015;36:

15 Updated metaanlysis n=20000 OR 0.90 (95% CI ) P=0.10

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

17 A change in the evidence. Routine thrombectomy compared to PCI alone did not reduce the primary endpoint with an increased risk of stroke Manual thrombectomy can no longer be recommended as a routine strategy Already reflected in the AHA/ACC guidelines with a Class III recommendation for routine use and IIB as bailout

18 A change in practice?

19 Local practice at Kings 57% 60 45% 50 % 37% 40 31% 30 C 20 S 10 %

20 Conclusion Yet another example of intuitive practice not borne out by the evidence? However, we have never really practiced of routine thrombectomy More restrictive practice of thrombectomy with large thrombus burden still appropriate (with some caution)

21 Thank You