Aspiration Thrombectomy With Primary PCI for STEMI: Review of the Data and Current Guidelines

Abstract: The presence of visible thrombus at the time of primary PCI for STEMI is associated with poor procedural and clinical outcomes. Aspiration thrombectomy has been used with primary PCI in an attempt to improve these outcomes. The TAPAS (Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction) Trial found that aspiration improved myocardial blush scores and ST-segment resolution (STR), and also was associated with lower mortality at 1 year. Four meta-analyses have shown improved measures of myocardial reperfusion (TIMI flow, myocardial blush, and STR) and improved procedural outcomes (reduced no-reflow and distal embolization), and three of four trials have shown reduced mortality. Aspiration thrombectomy has received a Class IIa indication with primary PCI in the recent ACC/AHA and ESC Guidelines. Unanswered questions include whether there is truly a mortality benefit with aspiration, which subgroups may and may not benefit from aspiration, and whether patients with large thrombus burden are better treated with mechanical thrombectomy. J INVASIVE CARDIOL 2010;22:2B–5B ————————————————————

Primary percutaneous coronary intervention (PCI) has greatly improved outcomes in patients with ST-elevation myocardial infarction (STEMI) and has become the preferred reperfusion strategy in patients with STEMI.

The presence of visible coronary thrombus at the time of primary PCI creates special challenges for the interventional cardiologist. Large thrombus burden is associated with an increased incidence of distal embolization and no-reflow and may limit reperfusion at the microvascular level as measured by myocardial blush and ST-segment resolution (STR). Large thrombus burden is associated with a greater frequency of major adverse cardiac events (MACE) and is a strong independent predictor of late mortality.¹

There are many ways to deal with coronary thrombus at the time of primary PCI: pharmacologic strategies (typically glycoprotein IIb/IIIa platelet inhibitors), embolic protection devices (filters and distal balloon occlusion with aspiration), mechanical thrombectomy (AngioJet Rheolytic Thrombectomy, Medrad Interventional/Possis, Minneapolis, Minnesota), and manual or aspiration thrombectomy devices (Figure 1). This paper reviews the role of manual thrombectomy in patients with STEMI.

Major Randomized Trials

The TAPAS (Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction) Trial was a landmark study that brought manual thrombectomy into the mainstream as adjuctive therapy with primary PCI for STEMI.² This trial randomized 1,071 patients with STEMI of less than 12 hours duration to primary PCI with manual thrombectomy with the Export catheter versus primary PCI alone. Aspiration was able to be performed in 90% of patients and retrieved visible thrombus or atheromatous material in 72% of patients. Aspiration resulted in significant improvement in the primary endpoint of frequency of myocardial blush grade 3 (MBG 3) (46% versus 32%, p70%) (57% versus 44%, pmortality reduction with aspiration thrombectomy at one year (see Figure 2).³ These results were impressive but not conclusive, since this was a single center study and since the study was not powered to detect differences in clinical endpoints, and mortality was not a pre-specified endpoint. The EXPIRA (Thrombectomy with EXPort catheter in Infarct-Related Artery during primary percutaneous coronary intervention) Trial randomized 175 patients with STEMI to primary PCI alone versus primary PCI with manual thrombectomy and showed a significant improvement in the primary endpoints of MBG 3 and complete STR.⁴ This study was unique in that it evaluated infarct size by MRI and found that microvascular obstruction extent was less in the acute phase with aspiration (1.7 g versus 3.7 g, p = 0.0003) and improvement in infarct size at 3 months was seen with aspiration (17% to 11%, p = 0.004) but not in the control group (14% to 13%, p=NS).

Meta-analyses

In addition to the two trials described above, there have been numerous small randomized trials evaluating manual thrombectomy, mechanical thrombectomy, and distal protection devices in patients undergoing primary PCI for STEMI. None of these trials has been adequately powered to evaluate clinical events. For this reason, a number of meta-analyses have been performed to help evaluate the role of manual thrombectomy (and other devices) as adjunctive therapy with primary PCI for STEMI. Bavry and Bhatt analyzed 13 trials with manual thrombectomy, 5 trials with mechanical thrombectomy (AngioJet, Medrad Interventional/Possis, Minneapolis, Minnesota, and X-sizer, EV3, Plymouth, Minnesota), and 9 trials with distal protection devices (Percusurge GuardWire, Medtronic; FilterWire, Boston Scientific, SpideRx, ev3; Angioguard, Cordis).⁵ Manual thrombectomy resulted in better myocardial blush scores and better STR; distal protection resulted in better myocardial blush but no improvement in STR; and mechanical thrombectomy resulted in no improvement in either myocardial blush or STR. Mortality was improved with aspiration, was neutral with distal protection, and was worse with mechanical thrombectomy (see Figure 3). The results of mechanical thrombectomy were driven primarily by the results of the AiMI (AngioJet in Myocardial Infarction) Trial.⁶ De Luca and colleagues analyzed nine randomized trials with 2,417 patients and compared PCI using manual thrombectomy with PCI alone.⁷ This meta-analysis found that manual thrombectomy was associated with more frequent TIMI 3 flow post-PCI (87% versus 81%, p8 Overall mortality and MACE were reduced with thrombectomy, but subgroup analyses found that these benefits were seen only in patients treated with manual thrombectomy and only in patients treated with glycoprotein IIb/IIIa inhibitors. Time to reperfusion, infarct artery, and initial TIMI flow did not have any significant impact on the benefit of thrombectomy. This meta-analysis has the advantage of a patient-level analysis, but also has the potential for bias, because only 11 of 17 trial investigators agreed to participate and provide data for the study. Also, categorization of the trial by Kaltoft et al as a mechanical thrombectomy trial may not be correct. Kaloft and colleagues used the Rescue catheter (Boston Scientific), which most would consider a manual or aspiration catheter, and aspiration thrombectomy with this device showed no clinical benefit and an increase in infarct size.⁹ Mongeon and colleagues performed a Bayesian meta-analysis of 21 randomized trials, 16 trials evaluating aspiration thrombectomy and 5 trials evaluating mechanical thrombectomy.¹⁰ The authors presented the results of their analyses with all 21 trials and also presented separately their results with the 16 trials with aspiration, and the results were similar. Results from the five trials with mechanical thrombectomy were not presented separately. In patients treated with aspiration, there were fewer distal emboli, less no-reflow, more frequent TIMI 3 flow post-PCI, more ST resolution >50%, and more MBG3 (see Figure 5). There were no significant differences in 30-day mortality. A summary of these 4 meta-analyses is shown in Table 1. All meta-analyses that evaluated surrogate endpoints of TIMI flow post-PCI, STR and MBG consistently showed superior outcomes with aspiration thrombectomy. The two meta-analyses that evaluated angiographic outcomes showed that aspiration thrombectomy reduced the frequency of distal emboli and no-reflow. Three of four analyses showed significantly lower mortality with aspiration thrombectomy, and the fourth trial showed no difference.

Limitations of Current Evidence

The evidence supporting the benefit of aspiration thrombectomy on surrogate outcomes (TIMI flow, MBG, and STR) and angiographic outcomes (distal emboli and no-reflow) is strong and convincing. The evidence supporting the benefit in mortality reduction is not as strong and has limitations. The TAPAS Trial, which showed a significant mortality reduction at 1 year with aspiration thrombectomy, was a single center study and was not powered to evaluate mortality.² The 46% reduction in mortality was certainly not expected and may have occurred by chance.³ Some of the benefit of aspiration may be from direct stenting, which was performed in 59% of aspiration patients, although this would not diminish the benefit of this overall approach. Meta-analyses certainly have limitations, one of which is selection bias for publication of positive trials. Negative trials are often not submitted for publication and when submitted may be less likely to be accepted for publication. There are certainly examples of treatments that were thought to be effective based on meta-analyses, but which were proven to be of no benefit when evaluated by a properly powered clinical trial. A prominent example is the use of magnesium for treatment of acute myocardial infarction. Magnesium was thought to reduce mortality with acute myocardial infarction based on a large meta-analysis but was found not to be effective in the large ISIS-4 trial.^11,12

Current Guidelines

Based on the TAPAS Trial and the above meta-analyses, the ACC/AHA Guidelines have given aspiration thrombectomy a Class IIa (Level of Evidence B) indication with primary PCI for STEMI, and the ESC Guidelines recently upgraded to Level of Evidence A.^13,14 This opinion states that “aspiration thrombectomy is reasonable for patients with STEMI undergoing primary PCI.” The committee did not feel the evidence for benefit on clinical outcomes was strong enough to warrant a Class I indication.

Unanswered Questions

All randomized trials with aspiration thrombectomy have been performed in “all comers” with STEMI, and it is not clear which subgroups may benefit most and which subgroups may not benefit at all. There are little data to help answer this question. Sianos and colleagues have shown that both angiographic outcomes and clinical outcomes are worse in patients with large thrombus burden.¹ Napodano and colleagues found that patients with RCA infarcts, long lesions and high thrombus score had the highest frequency of distal embolization.¹⁵ We might expect these subgroups to benefit most from thrombectomy, but data from the TAPAS trial do not support this.² Improvement in MBG with aspiration was no better in patients with RCA infarcts versus non-RCA infarcts and was no better in patients with visible thrombus compared with patients without visible thrombus. There was a trend for more benefit in patients with reperfusion time of less than 3 hours, but there were no differential benefits in patients stratified by pre-PCI TIMI flow. Overall, there are little current data to support selective use of aspiration thrombectomy in any subgroup of STEMI patients treated with primary PCI. Aspiration thrombectomy has limited ability to remove large thrombus burden and sometimes may be associated with incomplete thrombus removal, no-reflow, and/or distal emboli. There is previous and very recent evidence that mechanical thrombectomy may effectively improve outcomes in patients with large thrombus burden,^1,16 and whether mechanical thrombectomy is preferable to aspiration thrombectomy in patients with large thrombus burden remains an unanswered question.

References

1. Sianos G, Papafaklis MI, Daeman J, et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007;50:573–583.

2. Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 2008;358:557–567.

3. Vlaar PJ, Svilaas T, van der Horst IC, 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;371:1915–1920.

4. Sardella G, Mancone M, Bucciarelli-Ducci C, et al. Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size. The EXPIRA (Thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial. J Am Coll Cardiol 2009;53:309–315.

5. Bavry AA, Kumbhani DJ, Bhatt DL. Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: A comprehensive meta-analysis of randomized trials. Eur Heart J 2008;29:2989–3001.

6. Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction. J Am Coll Cardiol 2006;48:244–252.

7. De Luca G, Dudek D, Sardella G. et al. Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: A meta-analysis of randomized trials. Eur Heart J 2008;29:3002–3010.

8. Burzotta F, De Vita M, Gu YL, et al. Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: An individual patient-data pooled analysis of 11 trials. Eur Heart J 2009;30:2193–2203.

9. Kaltoft A, Bottcher M, Nielsen SS, et al. Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: A randomized, controlled trial. Circulation 2006;114:40–47.

10. Mongeon F-P, Belisle P, Joseph L, et al. Adjunctive thrombectomy for acute myocardial infarction: A Bayesian meta-analysis. Circ Cardiovasc Interv 2010;3:6–16.

11. Teo KK, Yusuf S, Collins R, et al. Effects of intravenous magnesium in suspected acute myocardial infarction: Overview of randomized trials. BMJ 1991;303:1499–1503.

12. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669–685.

13. Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009;120:2271–2306.

14. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: The Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2008;29:2909–2945.

15. Napodano T, Ramondo A, Tarantini G, et al. Predictors and time related impact of distal embolization during primary angioplasty. Eur Heart J 2009;30:305–31q3.

16. Antoniucci D and the JETSTENT Investigators. Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction: The JETSTENT Trial. Presented at the American College of Cardiology Scientific Sessions, Atlanta, Georgia, 2010.

———————————————————— From the LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina. The author reports no financial relationships or conflicts of interest regarding the content herein. Address for correspondence: Dr. Bruce R. Brodie, 313 Meadowbrook Terrace, Greensboro, NC 27408. E-mail: bbrodie@triad.rr.com