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In contrast, the European Ambulance Acute Syndrome Angiography (EUROMAX) trial [67] performed in 65 centers
demonstrated a reduced rate of non-CABG major bleeding with prehospital bivalirudin compared with prehospital heparin
and optional GPI (5.1% vs. 8.5%, P < .001). This reduction in bleeding with bivalirudin persisted regardless of GPI use
and regardless of arterial access route. However, again there was a significantly increased rate of acute stent thrombosis
(<24 h) (1.6% vs. 0.5%, P ¼ .02), although this increased risk was eliminated if the PCI dose of the infusion was
continued for several hours postprocedure.
Following EUROMAX and HEAT-PPCI, the large-scale multicenter BRIGHT trial was performed in which
patients with AMI were randomized to bivalirudin with a 3-h PCI dose postprocedure infusion versus UFH alone
versus UFH plus tirofiban (1:1:1 randomization) [68]. Bivalirudin resulted in lower bleeding compared with UFH alone
and UFH þ GPI, and no excess risk of acute stent thrombosis with bivalirudin was noted, presumably due to the 3-h postPCI high-dose bivalirudin infusion. It should be noted that clopidogrel was the only P2Y
inhibitor used in this study.
12
Finally, in the MATRIX trial, 7213 patients a t 105 centers with NSTE-ACS (n ¼ 3203) or STEMI (n ¼ 4010) were
randomized to heparin with optional G PI ver sus bi valir udin alone, with the latter group randomized again to either a
several-hour infusion of bivalirudin (low dose or high dose at operator discretion) or no infusion [69]. Bivalirudin
reduced all bleeding, major bleeding, and fatal bleeding and reduced all-cause mortality (2.3% vs. 3.7%, P ¼ .04). As in
EUROMAX and BRIGHT, acute stent thrombosis was slightly increased with bivalirudin, although not in patients who
received a several-hour PCI dose postprocedural infusion. Thus, these data collectively support the use of bivalirudin in
STEMI with a 3- to 4-h PCI dose postprocedural infusion, especially when GPI is being considered as adjunctive
therapy. In NSTE-ACS no postprocedural infusion is require d since acute stent thrombosis has not been reported to be
increased with bivalirudin in this setting. Of note, in the MATRIX, EUROMAX, and BRIGHT trials, the benefits of
bivalirudin in reducing bleeding and mortality were present in patients undergoing PCI with radial as well as femoral
access [69e71].
In the United States bivalirudin is the most widely used anticoagulant in the catheter lab. In Europe its use has b een
more selective. As of this writing, the ESC guidelines suggest bivalirudin in patients with NSTE-ACS undergoing PCI,
with a class I level of evidence A, while UFH is recommended for PCI if patients cannot receive bivalirudin (class I level of
evidence C). However, in STEMI the ESC guidelines favor UFH with or without a GPI (class I level of evidence C), while
bivalirudin with up to a 4-h post-PCI infusion is given a class IIa level A recommendation in this setting [51]. The
recommendations were finalized, however, before the MATRIX results were available.
FACTOR XA AND THROMBIN INHIBITORS IN ACUTE CORONARY SYNDROMES
Because factor Xa plays a central role in thrombosis, chronic inhibition of factor Xa may have a role in secondary
prevention after ACS. However, studies examining the utility of factor Xa inhibitors in ACS have report ed conflicting
results. In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial of 7932 patients with recent ACS
and at least two additional risk factors for recurrent ischemic events, apixaban did not provide any ischemic, thrombotic, or
mortality benefits, but did increase bleeding [70]. In the 15,526 patient ATLAS ACS 2-TIMI 51 trial, the addition of two
doses of rivaroxaban (2.5 and 5 mg, twice daily) was evaluated in ACS patients treated with aspirin therapy alone or DAPT
[62]. The doses when pooled together resulted in a reduced rate of the primary efficacy end point of death from car-
diovascular causes, MI, or stroke compared with placebo (8.9% vs. 10.7%, P ¼ .008). This benefit was realized at the
expense of a significantly increased rate of nonfatal bleeding (2.1% vs. 0.6%, P < .001), including cerebral hemorrhage
(0.6% vs. 0.2%, P ¼ .009). In addition, most ACS patients currently undergo PCI (requiring DAPT treatment) and, as
discussed earlier, adding a third (antithrombotic) agent to a DAPT regimen substantially increases major bleeding.
Treatment with the chronic oral factor IIa inhibitor dabigatran in the Randomized Dabigatran Etexilate Dose-Finding Study
in Patients With Acute Coronary Syndromes (REDEEM) trial [71], apixaban in APPRAISE-2 [70], and the thrombin
receptor antagonist vorapaxar in the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary
Syndrome (TRACER) [72] trial failed to demonstrate reductions in MACE in all studied patients and in those treated with
PCI, and, given the excess bleeding risk, demonstrated an unfavorable riskebene fit balance as studied. Moreover, the
riskebenefit profile of the novel oral anticoagulants with the more potent P2Y
(which have become the preferred agents in appropriate ACS patients undergoing PCI) is unknown, as the vast majority of
trial participants as of this writing have received clopidogrel. Further study is warranted before the use of these agents may
be routinely recommended in patients with ACS.
inhibitors such as prasugrel and ticagrelor
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Mechanical Methods of Thrombus Reduction
The ability to reduce intracoronary thrombu s burden wa s he rald ed as a pot entia l tar get in imp rovin g PCI techn ique in t he
setting of acute MI, particularly in the STEMI population, in which a significant majority (in excess of 90%) have
angiographic evidence of thrombus-laden IRA [73]. Therefore, thrombectomydmechanical thrombus extractiondhas
been cons idere d synergistic to PCI, by providing the PCI operator with the opportunity to reduce thrombus burden and
successfully complete PCI, thereby reducing a potential nidu s for acute stent thrombosis and theoretically reducing the
degree of distal embolization with concomitant effects on infarct size. This has ledtoanexpandingbodyofresearchin
the field.
Thrombus Aspiration Technology
Simple thrombectomy devices are intracoronary catheters with a central aspiration lumen through which the thrombus can
be extracted. These rapid-exchange devices are passed over an intracoronary guidewire into the IRA. Direct aspiration of
the occlud ing thrombus is performed under fluoroscopic guidance by slowly advancing and withdrawing the catheter
across (1) the lesion or (2) the area of greatest angiographic evidence of thrombus, while the catheter is attached to a
syringe on fixed negative pressure. After removal of the thrombus, the PCI proceeds with balloon dilatation and stent
deployment (see case example; Fig. 9.1).
(A) (B)
(C) (D)
FIGURE 9.1 Primary PCI with the adjunctive use of a thrombectomy device. (A) Occluded right coronary artery (RCA) (starred). (B) Residual
thrombus in distal vessel following wiring of vessel (starred). (C) Postthrombectomy with restoration of flow and reduction in radio-opaque thrombus.
(D) Final post-PCI result, with TIMI 3 flow. PCI, percutaneous coronary intervention; TIMI, thrombolysis in myocardial infarction.
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Both manual and rheolytic mechanical devices exist; manual devices involve the aspiration of the thrombus into a
syringe and include the Fetch 2 (Bayer), Export (Medtronic, USA), Pronto (Vascular Solutions, USA), QuickCat
(Spectranetics, Inc., USA), and Eliminate (Terumo). Although they are based on similar principles, differences are found in
the catheter material, aspiration lumen size, and specific configuration (Fig. 9.2).
Rheolytic devices include the AngioJet (Medrad, PA, USA) and X-Sizer (Ev3, Inc., MN, USA). They attempt active
thrombus fragmentation prior to aspiration. The AngioJet uses pressurized heparinized saline jets to create low-pressure
zones, thus creating a vacuum effect via which the thrombus can be drawn into the catheter. The X-Sizer device consists of a dual-lumen catheter. Similarly, a vacuum device harnesses the thrombus, allowing a helical cutter contained
inside the inner lumen to shear the thrombus (Fig. 9.3).
FIGURE 9.2 Examples of manual aspiration catheters. (A) Export catheter. (B) Pronto. (C) QuickCat. (D) Eliminate. (A) Medtronic, USA,
Reproduced from http://www.medtronic.com/for-healthcare-professionals/products-therapies/cardiovascular/catheters/aspiration-catheters/export-
advance/index.htm; (B) Vascular Solutions, USA, http://vasc.com/flash/Catalogs/INTL/#14; (C) Spectranetics, Inc., USA, http://www.spectranetics.
com/wp-content/uploads/D022220-00-QuickCat-Brochure.pdf; (D) Terumo, http://www.terumo-europe.com/en-emea/interventional-cardiology/
coronary-intervention-products/aspiration-catheter/eliminate%E2%84%A2-aspiration-catheter.
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FIGURE 9.3 Examples of rheolytic thrombus aspiration devices. (A) AngioJet. (B) Helical cutter as seen in the X-Sizer device. (A) MEDRAD, PA,
USA, Reproduced from http://www.bostonscientific.com/en-US/products/thrombectomy-systems/angiojet-ultra-coronary-thrombectomy-system.html; (B)
http://www.medscape.com/viewarticle/807098_3.
Clinical Trial Data of Thrombectomy in Myocardial Infarction
Initial evidence that emerged from single-center observational studies showed both the utility and the safety of thrombectomy in the setting of AMI. Van Ommen et al. provided observational insights on manual thrombus aspiration in
patients with angiographic evidence of significant thrombus burden following AMI [6]. Fifty-one lesions were treated in 50
patients with the Rescue catheter (Boston Scientific). Thrombotic material was removed in 48 of the 51 vessels. After
thrombectomy, 42 vessels showed TIMI grade 3 flow. There were two in-hospital deaths, both attributed to the patients’
clinical status and not the thrombectomy procedure itself. In the remaining 48 patients follow-up data were obtained from
47. At 6 months, 4 patients had angina pectoris with functional class II according to New York Heart Association (NYHA)
criteria, with the other 43 patients being symptom free.
Similarly, Rinfret and colleagues used the AngioJet rheolytic thrombectomy device in patients undergoing PCI, all
of whom had angiographic evidence of substantial thrombus in a culprit native artery or a saphenous vein graft
(SVG) of >2.0 mm [7]. One hundred twenty-six thrombectomy procedures were performed. TIMI grade 3 flow was
achieved in 83% of SVGs and 68% of native arteries. In terms of clinical outcomes, whereas 5 patients died, outcomes
for the remaining 119 patients were positive; none needed further revascularization procedures or urgent bypass surgery.
Six-month follow-up (available in 84% of patients) showed that 69% of patients were free from death, MI, target vessel
revascularization/restenosis, or ischemia.
Numerous other single-center studies continued to suggest improved clinical results with thrombectomy in the context
of acute MI. Burzotta et al. randomized patients to standard PCI or thrombectomy with the Diver aspiration catheter
(Invatec, Italy) [74]. Rates of myocardial blush grade (MBG > 2 68% vs. 44.9%, P ¼ .02) and ST resolution (STR)
(STR > 70% 58% vs. 36.7%, P ¼ .034) were both improved with thrombus aspiration. Dudek et al. randomized 72 patients presenting with STEMI to standard PCI or thrombectomy with the Rescue (Boston Scientific) thrombectomy catheter
[9]. While TIMI grade 3 flow was similar in both groups, STR was achieved in 68% of the thrombus aspiration group
versus 25% in the PCI group (P ¼ .005). Further, at 3 months follow-up, LVEF was higher in the thrombus aspiration
group than in those who underwent PCI alone (55.3 14.7% vs. 60.3 9.2%, NS). Silva-Orrego et al. also compared
standard PCI with thrombus aspiration prior to PCI. Both STR (68% vs. 50%, P < .05) and MBG (2.84 0.32 vs.
2.38 0.59, P < .001) were improved in the thrombus aspiration group [10].
Although these studies suggested improved procedural results with thrombus aspiration, they were in the context
of small observational series, with little or no clinical outcome data. Subsequently the TAPAS trial (Thrombus
Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study) was designed and reported
in 2008 [75].Itwasthefirst randomized trial comparing PCI versus routine use of thrombectomy together with PCI in
patients presenting with STEMI to evaluate whether thrombusaspirationresultedinimprovedmyocardialperfusion
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compared with PCI alone. Myocardial perfusion was assessed via the angiographic MBG scoring as a surrogate
of myocardial perfusion and microvascular function. Secondary end points were the postprocedural frequency of a
TIMI flow grade of 3, complete resolution of ST-segment elevatio n, the absence of persi sten t ST-segment deviation,
target-vessel revascula riza tio n, reinfarction, death, and the co mb inat ion of major adverse cardiac events by 30 days after
randomization.
One thousand seventy-one patients were eligible and randomly assigned to either the thrombus aspiration plus PCI
(n ¼ 535) or the standard PCI-only group (n ¼ 536). On the basis of the initial angiographic findings, 33 patients (around
6%) in each group did not undergo PCI. Within the thrombectomy arm, 55% (n ¼ 295) had thrombus aspiration followed
by stenting, and 29% underwent thrombus aspiration followed by balloon dilatation only. Ten percent crossed over to
conventional PCI without the use of the thrombectomy catheter, 12% underwent conventional PCI with additional
thrombus aspiration, and 6% had crossed over to thrombus aspiration and stenting.
There was a significant improvement in MBG scores between the two treatment arms, with an MBG score of 0 or 1
seen in 26% of the PCI-only group versus 17% in the thrombus-aspiration group (risk ratio 0.65, 95% CI 0.51e0.83,
P < .001).
In terms of secondary outcomes, complete STR occurred in 275 of the 486 patients (57%) in the thrombus-aspiration
group versus 219 of the 496 patients (44%) in the standard PCI group (risk ratio 1.28, 95% CI 1.13e1.45, P < .001).
Target-vessel revascularization occurred in 24 of 529 (4.5%) in the thrombus-aspiration group versus 31 of 531 (5.8%) in
the standard PCI group (risk ratio 0.77, 95% CI 0.46e1.30, P ¼ .34). Reinfarction occurred in 4 of 529 (0.8%) in the
thrombus-aspiration group versus 10 of 531 (1.9%) in the standard PCI group (risk ratio 0.4, 95% CI 0.13e1.27, P ¼ .11).
Major adverse cardiac events at 30 days were 6.8% in the thrombus-aspiration group versus 9.4% (n ¼ 50) in the standard
PCI group (risk ratio 0.72, 95% CI 0.48e1.08, P ¼ .12). Death occurred in 2.1% (n ¼ 11) of the thrombus-aspiration
group versus 4% (n ¼ 21), respectively (risk ratio 0.52, 95% CI 0.26e1.07, P ¼ .07).
The TAPAS study provided the first randomized assessment of routine use of thrombus aspiration in the setting of
STEMI, with a clear benefit observed in regard to improved MBG, though, importantly, no significant difference in harder
end points, such as all-cause mortality or MACE, at 30 days. A 1-year follow-up study also explored cardiac death and
reinfarction [76]. Cardiac death was seen in 3.6% (19 of 535 patients) in the thrombus-aspiration group versus 6.7% (36 of
536 patients) in the standard PCI group (HR 1.93, 95% CI 1.11e3.37, P ¼ .02). Thus, at 1 year, the use of thrombectomy
implied a significant reduction in mortality. The authors therefore proposed that routine use of thrombectomy was an
important adjunctive measure during PCI in the context of acute MI. Furthermore, it was suggested that thrombus aspiration prior to PCI was likely to provide improved reperfusion irrespective of age, sex, target vessel, preprocedure TIMI
flow, and visible thrombus on angiography.
Despite its promising headline results, the applicability of the TAPAS results was questioned and the clini ca l uptake
guarded because of a number of considerations. Although it was powered to detect significan t differen ce s in terms of
MBG, the study was underpowered to assess mortality. This is of particular concern given the role TAPAS had in
prompting thrombectomy as an adjuvant modality in national guidelines in the treatment of ACS. The study was also
conducted in a single high-volume center, with experienced operators, with rapid door-to-thrombectomy (median
28 min) and door-to-balloon time (m edia n 26 min). The widespread reproducibility of the results seen in the study was
questioned, and it was felt unlikely to represe nt “real-world” practice. Another consideration was the PCI technique
adopted in the study. As there was no mandate about how PCI was to be performed, there were considerable differences
between the two treatment groups. The t hr om bect om y arm had much lower stent usedonly 55% co mpa red with 90% in
the PCI-alone groupdwhich ma y have disadvantaged the thrombectomy arm in terms of increased restenosis rates.
Importantly, when stents were deployed, this was often performed with a direct stenting strategy without prior balloon
predilatation, as was standard i n the PCI-only arm, with the theoretical advant ag e of reducing distal embolization of
thrombotic material and therefore improving myocardial perfusio n. Systematic data on whether slow flow or no reflow
was increased in the balloon predilated IRA com pared with the thrombectomy as well as the stenting strateg y was not
collected and therefore this question cannot be definitely answered. However, evidence possibly reaffirming this may be
seen in the increased rate of persisting ST-segment elevation postprocedure in the PCI-alone group (59% vs. 47%,
P < .001). Moreover, the study was powered only to assess differences in angiographic MBG and not mortality. While
MBG r emai ns a useful clinical tool in assessing microcirculatory flow and t he refo re myocardial perfusion, it is limited
because of its subjective semiquantitative nature, and although the angiograp hic analysis was performed in a bli nde d
core laboratory setting, MBG remains an operator-dependent dataset and is inherently prone to bias. Most importantly,
however, is that the power of the study was based upon perturbations in MBG between groups, and not differences
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in survival, which was a secondary end point. Therefor e any inf er ence made from the improved 1-year mortality
in the thrombectomy-treated arm must be treated with caution since the study was not powered to answer this
particular question.
In contrast to the TAPAS study, Kaltoft et al. observed, in a small single-center trial, that thrombectomy pre-PCI
provided limited benefit to routine PCI care [77]. The Danish group randomized patients presenting within 12 h of
STEMI to receive PCI alone or thrombus aspirati on in addition to PCI. Myocardial salvage was measured by sestamibi
SPECT scan, and calculated as the difference between area at risk and final infarct size determined after 30 days. There was
no difference detected between the two groups in terms of myocardial salvage (13% in thrombectomy group vs. 18% in
PCI-only group, p ¼ 0.12). This study went further to suggest that adjunctive thrombectomy had the potential of causing
harm, with infarct size found to be larger in the thrombectomy group compared with the PCI-only group (median 15% of
left-ventricular mass [interquartile range (IQR) 4%e25%] vs. median 8% [IQR 2%e18%], P ¼ .004).
Numerous other smaller-scale tria ls also questione d the validity of thrombectomy in the context of STEMI. In
the INFUSE-AMI (Intracoronary Abciximab Infusion and Aspiration Thrombectomy in Patients Undergoing Percutaneous Coronary Intervention for Anterior ST Segme nt Elevation Myocar dial Infarction) mul ticen ter trial [78],452
patients presenting within 4 h of STEMI se conda ry to proximal or mid-left-anterior descending artery occlusion were
randomized in an open-label, 2 2 factorial design to (1) intracoronary abciximab versus no abciximab and
(2) thrombus aspiration versus no thrombus aspiration. Patients were thus equally randomized into one of four groups:
(1) thrombus aspiration followed by intracoronary bolus abciximab, (2) thrombus aspiration without abciximab, (3)
intracoronary bolus abciximab without aspiration, and (4) no abciximab and no aspiration. For patients randomized to
thrombus aspiration, a 6-Fr Export catheter (Medtroni c) was used. Cardiac MRI was used to assess primary outcom es of
infarct size (percentage of total left-ventricular mass) at 30 days. Patients in the thrombus-a spir at ion group showed no
significant difference from the nonaspiration group in terms of infarct size at 30 days, absolute infarct mass, or abnormal
wall motion score.
It was therefore apparent that questions remained unanswered about the utility of thrombectomy in the setting
of AMI. This led to the TASTE (Thrombus Aspiration in ST-Ele vati on in Myocardial Infarction in Scandinavia)
trial [79]. In this study 30-day and 1-year mortality was examined in patients treated with routine thrombus aspiration
and then PCI and compared with a PCI-only strategy. Patients prese ntin g with STEMI to any on e of 32 Scandinavian
centers participating were enrolled v ia the Swedish Coronary Angiography and Angioplasty Registry. Patients
were diagnosed via ECG and excluded because of an urgent need for coronary artery bypass surgery or an inability to
provide informed consent. Ther e was a planned enrollment of 5000 p atie nt s: the authors based this on preexistin g
mortality data for patients undergoing PCI of 6.3%, meaning 456 events were required for an 80% power. A total of
7244 patients wer e randomized to thrombus a spir ation followed by PCI (n ¼ 3621) or standard PCI only (n ¼ 3623). At
30 days, there was no significant difference in mortality rates: 2.8% in the thrombus-aspiration group versus 3.0% in the
PCI-only group (HR 0.94, 95% CI 0.72e1.22, p ¼ 0.63). Furthermore, no difference was observed in rates of
rehospitalization related to reinfarction: 0.5% versus 0.9%, respectively. In terms of all-cause survival, at 1 year, there
was no difference or trend toward improved outcomes with the routine use of thrombectomy. Moreover, there was no
difference across the two groups in rates of stent thrombosis, target-vessel revascularization, nor stroke or neurological
complication. There was no difference in length of hospital stay. The authors concluded that there was no significant
bene
fit from the routine use of thrombus aspiration in the setting of AMI, evidenced by the lack of significant difference
in outcomes.
The TASTE trial therefore provided the first adequately powered study assessing the routine use of thrombectomy in
AMI, providing important insights into the ease of use and safety of thrombus aspiration in this setting. The trial
recruited a large number of acutely unwell patients very e fficiently. However, to allow adequate, efficien t recruitment to
the study, the study used a registry-based randomized control trial (RCT) model, rather than the more traditional RCT
model. Therefore, it is important to recognize differences between traditional RCTs and registry-based RCTs. For
example, the TASTE trial did not require central data moni toring nor the presence of an adjudicating committee.
Additionally, operators were advised to consider randomization only a fter patient and procedural data were entered into
the database. It is apparent that the study structure, with patient selection via national data registries, could have led to
the potential of selection bias.
The available trial data thus far suggested that there was no benefit from thrombectomy, but addit ionally, there were
concerns that routine thrombectomy was associated with an increased adverse event rate, in particular an excess of periprocedural stroke. De Luca et al. performed a meta-analysis of the data analyzing 21 observational and randomized
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datasets involving in excess of 4500 patients [80]. The authors exami ned patients treated with both manual and mechanical
thrombectomy. Whereas manual thrombectomy was associated with improved postprocedural TIMI grade 3 flow and STR,
the thrombectomy group showed no reduction in 30-day mortality or reinfarction. There was also a signal of increased
stroke in those treated with thrombectomy, though not statistically significant (P ¼ .06). More recently, Elgendy et al.
performed a meta-analysis of randomized trials assessing the benefit of aspiration thrombectomy in PPCI [81]. Seventeen
trials were available for analysis. Compared with conventional PCI, aspiration thrombectomy was not associated with a
significant reduction in the risk of mortality (2.8% vs. 3.2%, respectively; RR 0.89, 95% CI 0.76e1.04, P ¼ .13), reinfarction (1.3% vs. 1.4%; RR 0.93, 95% CI 0.73e1.17, P ¼ .52), combined mortality or reinfarction (4.1% vs. 4.6%; RR
0.9, 95% CI 0.79e1.02, P ¼ .11), or stent thrombosis (0.9% vs. 1.2%; RR 0.82, 95% CI 0.62e1.08, P ¼ .15) (see
Fig. 9.3). As in De Luca’s meta-analysis, a nonsignificant increase in the risk of stroke was observed (0.6% vs. 0.4%; RR
1.45, 95% CI 0.96e2.21, P ¼ .08).
Results from large trials were thus conflicting; TAPAS demonstrated increased MBG and lower mortality with
thrombectomy in an underpowered study; meta-analyses suggested a potential increased risk of periprocedural stroke,
while TASTE showed no reduction in mortality either at 30 days or at 1 year. These differing findings highlighted the need
for a larger-scale, multicenter trial of routine thrombectomy during PPCI to reassess its efficacy and safety.
This impetus led to the design of TOTAL (Trial of Routine Aspiration Thrombectomy with Percutaneous Coronary
Intervention [PCI] Versus PCI Alone in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary
PCI) [82]. This was an international, multicenter, parallel randomized trial with blinded outcome assessment that sought to
compare PCI with adjunctive thrombectomy versus PCI alone in patients undergoing PPCI in the context of STEMI. To
ensure adequate power, the calculated sample size was adjusted to cover nonadherence rates, and was increased by another
8% to account for patients randomized but who would not undergo PCI.
A total of 10,732 patients presenting with STEMI within 12 h of symptom onset deemed eligible for PCI were ran-
domized in a 1:1 ratio to each study arm. The primary outcome was a composite of death from cardiovascular causes,
recurrent MI, cardiogenic shock, or new or worsening heart failure (NYHA IV) within 6 months. Additional secondary
outcomes included stent thrombosis, target-vessel revascularization, and CV death within this time frame.
The primary outcomes, including CV death, recurrent MI, cardiogenic shock, or the development of NYHA heart
failure class IV, were witnessed in 6.9% of patients in the thrombectomy plus PCI group versus 7.0% in the standard PCI
group (HR 0.99, 95% CI 0.85e1.15, P ¼ .86). Cardiovascular mortality between the two groups was the same at 30 days
(2.3% in thrombectomy group vs. 2.8% in standard PCI group, HR 0.83, 95% CI 0.65e1.05, P ¼ .13) and at 180 days
(3.1% vs. 3.5%; HR 0.9, 95% CI 0.73e1.12, P ¼ .34).
In terms of electrocardiographic outcomes, 27% of patients in the thrombectomy group had incomplete STR (less than
70% ST resolution) compared with 30% in the PCI group (P < .001). Rates of TIMI 3 flow were equal in both groups
(93.1% in both groups, P ¼ .12), and no
flow (2.4% vs. 2.8%, P ¼ .28) was also similar across both groups. The
thrombectomy group saw reduced rates of distal embolization (1.6% vs. 3.0%, P < .001). Importantly, no differences were
observed between the groups for dissection of target vessel or left main coronary vessel, nor thrombus embolization to the
left main artery.
Rates of stroke were marginally higher in the thrombectomy group; at 30 days, 0.7% patients in the thrombectomy
group had suffered stroked compared with 0.3% in the standard PCI group (HR 2.06, 95% CI 1.13e3.75, P ¼ .02). At
180 days, 52 patients (1%) in the thrombectomy group had suffered stroke versus 25 patients (0.5%) in the standard PCI
group (HR 2.08, 95% CI 1.29e3.35, P ¼ .002). While the incidence of periprocedural stroke was low, it conferred a poor
prognosis, with a mortality of 30.8% within 180 days compared with those without a stroke (3.4%, P < .001). To understand why the thrombectomy group witnessed increased rates of stroke, the authors performed a further analysis. At
180 days, there was an increase in both ischemic stroke (37 [0.7%[ vs. 21 [0.4%]; HR 1.76, 95% CI 1.03e3.00) and
primary hemorrhagic stroke (10 [0.2%] vs. 2 [0.04%]; HR 4.98, 95% CI 1.09e22.7). It was suggested that the increase in
ischemic stroke may have arisen from embolization of thrombus from the coronary to the systemic va sculature during
instrumentation. The fact that more aggressive guidewire manipulation is sometimes warranted in thrombectomy, together
with the fact that procedural times were longer in the treatment arm (39 vs. 35 min, P < .001), may have increased the risk
of dislodgment of atheromatous material from the aorta. There is no clear explanation as to the cause of increased rates of
hemorrhagic stroke. There were no differences in the dose of UFH during PCI, nor were there differences in the use of
P2Y
inhibitors or oral anti coagulants, either at discharge or at follow-up. It was suggested that, in view of the small
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number of hemorrhagic events, the finding may have been due to chance. The final conclusion was that there was a higher
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(A)
(D)
(C)
(B)
(E)
FIGURE 9.4 Use of laser in a STEMI case. (AeC) Angiographic and OCT images showing a large thrombus burden in the left anterior descending
artery (LAD) prior to laser (asterix). (D) Postlaser OCT imaging confirming a reduction in thrombus. (E) Post-PCI result with TIMI 3 flow (arrows
highlight OCT image at angiographic point). OCT, optical coherence tomography; PCI, percutaneous coronary intervention; STEMI, ST-segment
elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction.
rate of stroke evident when routine thrombectomy was employed and that further thrombectomy trials were needed to more
meticulously ascertain the cause and consequence of stroke to evaluate the procedure’s safety.
Aside from the risk of stroke, the authors of the TOTAL trial concluded that a strategy of routine manual thrombectomy
during PPCI did not reduce the risk of CV death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure
compared with standard PCI alone. Although based on an open design, which allows for selection bias, TOTAL was a
large trial, adequately powe red, with results that corroborated previous RCTs, reaffirming the limited role of routine use of
thrombectomy. The authors therefore suggested that while the evidence does not support “up-front” thrombectomy as a
routine part of PCI, it is a useful adjunct when traditional PCI is not successful, as seen in the 7% of PCI-only patients in
TOTAL who received bailout thrombectomy and had good clinical outcomes.
138 Cardiovascular Thrombus
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Excimer Laser Coronary Atherectomy
Laser devices harness light of a specific wavelength to generate a unidirectional beam of high-intensity light that can be
directed toward an object of interest. The wavelength of the emitted light is used to categorize the type of laser. The depth
of penetration of the laser is directly related to its wavelength, with laser in the ultraviolet range (shorter wavelength)
having less depth of penetration, less heat production, and less unwanted tissue damage. The excimer (excited dimer) laser
emits light at 308 nm with a typical absorption depth of 50 mm. The original Nd-YAG and argon medical lasers emitted
infrared light continuously, which resulted in excess heat production and tissue injury and inflammation, explaining the
high rates of thrombosis and vessel damage/dissection. The excimer laser systems deliver the light in short bursts or
“pulses” during a period of between 5 and 10 s. This approach minimizes heat production and allo ws the emitted energy to
disperse during the “off” period. The number of pulses generated during 1 s (known as the frequency) can be modified at
the operator’s discretion. Fluence refers to the amount of energy delivered in mJ/mm
off repetition rate per second. These values are typically presented as numerical values with fluence first and frequency
second, e.g., 60/40.
Excimer laser tissue ablation within the cardiovascular system is mediated through three distinct mechanisms: photothermal, photochemical, and photomechanical. UV light is rapidly and effectively absorbed by intravascular tissue and
thrombus, and the absorbed light breaks carbon bonds, so weakening the structure of the cells (photochemical). Delivery of
UV light aggravates molecular bonds, which elevates the temperature of intracellular water, eventually producing water
vapor, causing the cells to rupture. The generation of a vapor bubble cloud at the tip of the catheter enables controlled
disruption of the atherosclerotic material (photothermal). Expansion and implosion of these vapor bubbles generates the
photomechanical effect as the pressure is released from the vapor bubble, further disrupting the obstructive intravascular
material as well as sweeping the freed particles downstream (photomechanical). The vast majority of the fragments
2
and the frequency relates to the on/
(A)
Ai
(B)
Bi
Ci
(C)
Cii
Ciii
Ciii
Cii
Ci
FIGURE 9.5 Use of laser in a thrombotic lesion prior to BVS implantation. (A and B) Angiographic images of thrombotic lesion with corresponding
OCT images. (C) Post-PCI OCT images confirming good angiographic and OCT results following BVS implantation. OCT, optical coherence tomography; PCI, percutaneous coronary intervention; BVS, bioresorbable vascular scaffold.
Acute Myocardial Infarction: STEMI and NSTEMI Chapter | 9 139
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(A) (B) (C)
i
D
i
F
(D) (E) (F)
Thrombcat
Filterwire EZ
FIGURE 9.6 Use of thrombectomy and FilterWire EZ in a heavy thrombus burden in RCA during a STEMI. (A and B) Angiograms showing
heavy thrombus within vessel. (C) Residual thrombus after stent deployment. (D and E) FilterWire EZ and Thrombcat thrombectomy in use. (F) Post-PCI
result. PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; right coronary artery (RCA).
TM
TM
released during laser atherectomy are <10 mm in diameter and are easily filtered by the reticuloendothelial system
downstream, which avoids mic rovascular obstruction and no-reflow phenomena.
Laser energy interacts with two essential compo nents of thrombus: fibrin and platelets. Pulsed-wave lasers such as the
mid-infrared holmium and the ultraviolet excimer create an acoustic shock wave that propagates along the irradiated vessel.
These waves carry a dynamic pressure front toward the fibrin mesh within the thrombus. This process disrupts and breaks
the fibrin fibers, resulting in fibrinolysis, and thereby reduces thrombus size [83]. Clinically, the excimer laser has been
found to be a useful interventional tool for targeted thrombus removal strategy particularly given that thrombus has an
affinity for absorption of light within the UV spectrum [84]. This laser also alters the aggregation kinetics of platelets,
leading to reduced platelet force development and inhibition of platelet activity. This phenomenon of platelet stunning is
dose dependent and most pronounced at high fluence levels such as 60 mJ/mm
Excimer laser coronary atherectomy (ELCA) is therefore a potentially beneficial revascularization modality given the
potential for effective thrombus remo val [86], promotion of fibrinolysis [87], platelet-stunning effects [88], and
concomitant plaque debulking [89]. For illustrative purposes, Figs. 9.4e9.8 highlight clinical cases in which laser has been
adopted with a successful clinical outcome.
However, randomized clinical data regarding the use of ELCA in AMI are extremely limited. The largest study to date,
the CARMEL (Cohort of Acute Revascularization of Myocardial Infarction with Excimer Laser) [85] multicenter registry,
enrolled 151 AMI patients from six centers in the United States, one in Canada, and one in Germany. Twenty percent of the
2
[85].
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