Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy

Selected in The New England Journal of Medicine by G. Harris

References

Authors

Sanjit S. Jolly, M.D., John A. Cairns, M.D., Salim Yusuf, M.D., D.Phil., Brandi Meeks, M.Eng., Janice Pogue, Ph.D., Michael J. Rokoss, M.D., Sasko Kedev, M.D., Ph.D., Lehana Thabane, Ph.D., Goran Stankovic, M.D., Raul Moreno, M.D., Ph.D., Anthony Gershlick, M.B., B.S., Saqib Chowdhary, M.D., Ph.D., Shahar Lavi, M.D., Ph.D., Kari Niemelä, M.D., Philippe Gabriel Steg, M.D., Ivo Bernat, M.D., Ph.D., Yawei Xu, M.D., Ph.D., Warren J. Cantor, M.D., Christopher B. Overgaard, M.D., Christoph K. Naber, M.D., Ph.D., Asim N. Cheema, M.D., Ph.D., Robert C. Welsh, M.D., Olivier F. Bertrand, M.D., Ph.D., Alvaro Avezum, M.D., Ph.D., Ravinay Bhindi, M.B.B.S., Ph.D., Samir Pancholy, M.D., Sunil V. Rao, M.D., Madhu K. Natarajan, M.D., Jurriën M. ten Berg, M.D., Ph.D., Olga Shestakovska, M.Sc., Peggy Gao, M.Sc., Petr Widimsky, M.D., D.Sc., and Vladimír Džavík, M.D. for the TOTAL Investigators

Reference

N Engl J Med 2015; 372:1389-1398

Published

March 2015

Link

Access the Abstract

My Comment

Background

The presence of intracoronary thrombus is associated with an increased risk of complete vessel occlusion during or after balloon angioplasty, death, myocardial infarction and emergency bypass surgery (Mabin,TA; Holmes,DR JACC 1985,Febr), (Singh,M; Berger,PB; Am. J. Cardiol. 2001).

The TOTAL trial sought to establish whether in patients with STEMI, the benefits of routine manual thrombectomy with PCI, are superior to PCI alone.

In the TAPAS trial (N=1071), NEJM 2008, (unselected group of patients presenting with STEMI), the use of mechanical thrombectomy decreased both cardiac death (3.6% vs. 6.7%, P=0.02) and combination of mortality and non-fatal myocardial infarction, at 1 year. An improved myocardial blush score was also demonstrated. The majority of these patients received a GP IIbIIIa inhibitor.

Both the JETSTENT trial and the INFUSE AMI (patients were on bivalirudin) trial, could show no benefit in using routine mechanical thrombectomy in these patients.

An analysis performed by Barry & Bhatt (European Heart Journal 2008), demonstrated that mechanical thrombectomy improved neither myocardial blush nor St segment resolution.

The EXPIRA trial demonstrated improved, myocardial blush and complete ST segment resolution, when using an Export catheter in patients with STEMI. Further, micro vascular integrity was shown by MRI to be superior in the thrombectomy group, as well as improved limitation of infarct size at 3 months.

The TASTE trial demonstrated a reduction in stent thrombosis and recurrent myocardial infarction at 30 days. However no reduction in mortality at both 30 days and one year.

The 1e outcome in the TOTAL trial was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock or New York Heart Association (NYHA) class IV heart failure within 180 days.

Major findings

  • There was no difference in the 1e outcome between the two groups (6.9% of patients in the thombectomy group vs. 7.0 % of patients in the PCI alone group; P=0.86).
  • However there was an increased stroke rate, 0.7% thrombectomy vs. 0.3% PCI only: P=0.02). Despite attempts to ensure that the guide catheters were fully engaged into the coronary ostium.
  • Also no difference in cardiovascular death occurred in 3.1% thrombectomy vs. 3.5% PCI only: P=0.34).
  • The 1e outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%: P=0.95. Thus no difference.
  • Incomplete ST-segment resolution (less than 70%) was 27.0% in the thrombectomy group vs. 30.2% in the PCI-alone group (P<0.001).
  • TIMI 3 flow post PCI was the same in both groups.
  • Rate of distal embolization was reduced with thrombectomy (1.6% vs. 3.0%, P< 0.001).

My comment

The data from the TOTAL trial is consistent with that of the TASTE trial. It is important to note that bailout thrombectomy was allowed in the PCI alone arm (if there was failure; defined as TIMI flow 0 or 1, with a large thrombus after balloon predilation or the persistence of a large thrombus post stent deployment.

As pointed out in the NEJM editorial, the event rates in the control arm were half that which were originally considered for power calculation.

There was no difference in the subgroup analyses when differentiating thrombus burden, time of symptom onset, anterior vs. non-anterior MI, initial TIMI flow or age (younger or older than 65 years).

The TOTAL trial was not adequately powered to assess for this stroke difference and this difference may be due to chance.

Although thrombus aspiration is often viewed as a strategic tool to restrict the damage in the distal microvasculature, post STEMI, maybe its main benefit, is in reducing a large thrombus burden prior to stenting, and thereby preventing stent mal apposition and stent thrombosis.

As far as improving distal microvasculature blood flow, in STEMI patients with a high thrombus burden, interventions such intracoronary abciximab (INFUSE-AMI trial – at best, modest improvement) or use of specialized stents e.g. the MGuard Embolic Protection Stent may have more value? Another strategy to consider is the use of percutaneous ballon angioplasty alone, with flow restoration of at least TIMI 2 flow coupled to the use of Prasugrel rather than Clopidogrel, in patients with low bleeding risk, for a few days and then repeat angiography a few days later (same admission), with the view to reassess the lesion and possible stenting. This also allows some time time for the spasm to settle, but it is imperative, not to forget to inject nitrates prior to stenting these high thrombus lesions.

In my view, there is currently not enough data to justify the practice of routine mechanical thrombectomy in patients presenting with STEMI, however, it may be reasonable (class IIb) to consider the use of mechanical thrombectomy as a bail out procedure (as is reflected in the 2014 ESC guidelines), ideally with a GP IIbIIIa inhibitor (class IIa in current ESC guidelines).

Having said that, remember whilst managing your acute STEMI patient with a large thrombus load, not all of them fell within the inclusion criteria of the trials. This point was highlighted by Prof. Jean Marco, at the recent AfricaPCR meeting.

3 comments

  • ahmed kamel 21 Apr 2015

    With all my respect to the conflicting trial results regarding TIMI flow .I think that the no reflow phenomenon should be avoided specially if there is a high thrombus burden so i prefere thrombectomy.

  • ahmed kamel 21 Apr 2015

    With all my respect to the conflicting trial results regarding TIMI flow .I think that the no reflow phenomenon should be avoided specially if there is a high thrombus burden so i prefere thrombectomy.

  • David Look 02 Jun 2015

    Did TA help TOTAL’s PCIs run smoother? • Better ST segment resolution &lt; 70% p &lt; .001 • Distal embolization reduction p &lt; .001 • More direct stenting (17%) p &lt; .001 sizing ease, apposition? • High cross over / bail out (~ 1 in 10) • Exclusion of tough cases (a yes vote) • Reduced GPI use ($) p &lt; .0002 Bonus $: • Fewer, shorter stents (from TASTE data only p &lt; .02, p &lt; .05) and Jury is not out on TASTE yet: 18 mo. PCR poster update on TASTE =&gt; 180 day composite – reduced “Cardiac death, cardiogenic”, p = .058 - near ss mortality benefit will time improve? STEMI patient heterogeneity convolutes any PCI mortality signal -- Onset 2 balloon, comorbidities, lesion type, multi vs. single…etc.? Blinding, Inclusion/procedural bias, suspicious populations in both trials --Low events (1/3 of its parallel registry in TASTE), no tracking in TOTAL --Relevance of routine use vs. selective, large cross-over/bail, G2Bs use p=.0002?