Prof Juan Carlos Kaski, St George's, University of London, UK

Treatment of patients with STEMI aims predominantly at promptly restoring normal coronary blood flow using percutaneous coronary intervention (PCI). In many patients, however, microvascular obstruction (MVO) may develop despite successful epicardial coronary artery revascularisation. Data indicate that MVO leading to poor blood flow in the MI culprit artery is associated with increased infarct size and death. Results of the TAPAS study (1,2) led to the recommendation by both ESC and ACC/AHA guidelines that coronary artery thrombus aspiration should be used as an adjunctive therapy during primary PCI for STEMI (IIa class, level of evidence B). (3) The TAPAS study has been however criticized particularly in relation to having been underpowered.

Recently, The TOTAL study (4), involving 10,732 STEMI patients presenting to hospital within 12 hours from the beginning of symptoms, showed that routine manual thrombus aspiration during primary PCI did not reduce cardiovascular events at 1 year of follow up. Moreover –and of major clinical relevance- thrombectomy in this study was associated with a significantly increased risk of stroke.  Indeed, although the proportion of patients reaching the primary cardiovascular endpoint, i.e. cardiovascular death, MI, heart failure and cardiogenic shock was similar (8%) in both study arms, the risk of stroke was significantly higher (1.2%) in the thrombectomy arm compared with that (0.7%) in patients randomized to PCI alone (hazard ratio 1.66; 95% CI 1.10–2.51).  These findings challenge the results reported by the TAPAS study (1,2) and furthermore warn about a significantly increased risk of stroke in patients undergoing manual thrombus aspiration.

The stroke data in TOTAL are in agreement with results in a meta-analysis of 20 randomized trials (n=21,173 patients), published as part of the TOTAL manuscript in the Lancet (4). The meta-analysis reports the occurrence of stroke in 0.9% of patients in the manual aspiration arm versus 0.6% of patients in the PCI alone arm (OR 1.43; 95% CI 1.03–1.99).

Several important clinical implications can be derived from the results of the TOTAL study, including the following:

  1. Lack of benefit regarding cardiovascular endpoints – a finding also confirmed by the results of the meta-analysis mentioned above and those of a smaller study published recently in JACC Cardiovascular Intervention (5).
  2. Evidence of harm, as suggested by the increased risk of stroke with the routine use of thrombus aspiration
  3. The need for national and international guidelines to be issued regarding thrombus aspiration in STEMI patients undergoing PCI, as this practice is now common in catheter labs worldwide.

References

  1. Svilaas T et al. Thrombus Aspiration during Primary Percutaneous Coronary Intervention. New England Journal of Medicine. 2008;358(6):557-67.
  2. Vlaar PJ et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet. 2008;371(9628):1915-20.
  3. Steg PG et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569-619. Epub 2012/08/28.
  4. Jolly SS et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomized TOTAL trial. Lancet 2015; DOI: 10.1016/S0140-6736(15)00448-1.
  5. Desch S et al. Thrombus aspiration in patients with ST-elevation myocardial infarction presenting late after symptom onset. JACC Cardiovasc Interv 2015; DOI: 10.1016/j.jcin.2015.09.010. Available at:

http://interventions.onlinejacc.org/journal.aspx.

Cardio Debate Expert Comments

Manual thrombus aspiration in STEMI patients: TOTAL trial substudies

The TOTAL study (Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI) randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone1,2. The primary outcome 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. The key safety outcome was stroke within 30 days.

There were no diferences in the primary endpoint between both groups, however, the stroke within 30 days was higher in the thrombectomy group compared to the PCI-alone group (0.7% vs 0.3%; hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). One year follow up data published in Lancet3, showed again no differences in efficacy, but stroke rate within 1 year occurred in 1.2% of the cases in the thrombectomy group compared to 0.7% in the PCI alone group (HR 1.66 [95% CI 1.10–2.51], p=0.015).

Further subgroup analysis of the TOTAL trial have been recently published and added more information to the controversial role of thrombectomy in the STEMI setting.

Stroke in the TOTAL trial4

A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed.

As previously pointed out, stroke within 30 and 1 year, the primary safety outcome, were both increased. The difference in stroke was apparent within 48 h. There was an increase in strokes within 180 days with minor or no disability and in strokes with major disability or fatal. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03 – 3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09 – 22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P= 0.001).

The optical coherence tomography (OCT) substudy5

This sub analysis compared the thrombus burden at the culprit lesion in both treatment arms. OCT was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. The results showed that manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

The angiographic substudy6

This substudy investigated whether manual thrombectomy compared to PCI alone impact on myocardial blush grade 0/1, final TIMI flow and distal embolization. It also assessed the relationship among these variables and mortality.

The results showed that routine thrombectomy did not result in an improvement in final myocardial blush or TIMI flow following PCI for STEMI. This strategy reduced angiographic distal embolization and this variable was independently associated with mortality in multivariable analysis.

CONCLUSION

Considering all these information, a strategy of routine thrombectomy can not be recommended given:

  1. The lack of efficacy. Thrombectomy failed to show benefit when cardiovascular enpoints were compared.
  2. The increased stroke rate observed and its direct impact on mortality.

Further trials are needed to identify the role of thrombectomy in STEMI patients. Distal embolization is an important surrogate endpoint which is less subjective than blush and should be considered in future trials evaluating therapies for STEMI management.

REFERENCES

1.- Jolly SS, Cairns J, Yusuf S, et al. Design and rationale of the TOTAL trial: a randomized trial of routine aspiration ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in patients with ST-elevation myocardial infarction undergoing primary PCI. Am Heart J. 2014;167:315-321.

2.- Randomized trial of primary PCI with or without routine manual thrombectomy. Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, Kedev S, Thabane L, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemelä K, Steg PG, Bernat I, Xu Y, Cantor WJ, Overgaard CB, Naber CK, Cheema AN, Welsh RC, Bertrand OF, Avezum A, Bhindi R, Pancholy S, Rao SV, Natarajan MK, ten Berg JM, Shestakovska O, Gao P, Widimsky P, Džavík V; TOTAL Investigators. N Engl J Med. 2015 Apr 9;372(15):1389-98. doi: 10.1056/NEJMoa1415098. Epub 2015 Mar 16.

3.- Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial. Jolly SS, Cairns JA, Yusuf S, Rokoss MJ, Gao P, Meeks B, Kedev S, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemela K, Bernat I, Cantor WJ, Cheema AN, Steg PG, Welsh RC, Sheth T, Bertrand OF, Avezum A, Bhindi R, Natarajan MK, Horak D, Leung RC, Kassam S, Rao SV, El-Omar M, Mehta SR, Velianou JL, Pancholy S, Džavík V; TOTAL Investigators. Lancet. 2015 Oct 12. pii: S0140-6736(15)00448-1. doi: 10.1016/S0140-6736(15)00448-1.

4.- Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction. Jolly SS, Cairns JA, Yusuf S, Meeks B, Gao P, Hart RG, Kedev S, Stankovic G, Moreno R, Horak D, Kassam S, Rokoss MJ, Leung RC, El-Omar M, Romppanen HO, Alazzoni A, Alak A, Fung A, Alexopoulos D, Schwalm JD, Valettas N, Džavík V; TOTAL Investigators. Eur Heart J. 2015 Sep 14;36(35):2364-72. doi: 10.1093/eurheartj/ehv296. Epub 2015 Jun 29.

5.- Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial. Bhindi R, Kajander OA, Jolly SS, Kassam S, Lavi S, Niemelä K, Fung A, Cheema AN, Meeks B, Alexopoulos D, Kočka V, Cantor WJ, Kaivosoja TP, Shestakovska O, Gao P, Stankovic G, Džavík V, Sheth T. Eur Heart J. 2015 Aug 1;36(29):1892-900. doi: 10.1093/eurheartj/ehv176. Epub 2015 May 20.

6.- Overgaard C. Myocardial blush and microvascular reperfusion following manual thrombectomy during PCI for STEMI: insights from the TOTAL trial. Program and abstracts of EuroPCR 2015; May 19-22, 2015; Paris, France. Hot Line–Primary PCI and STEMI in Practice. http://www.pcronline.com/EuroPCR/EuroPCR-2015/Hot-line-Primary-PCI-and-STEMI-in-practice. Accessed December 9th, 2015.