Adjunctive thrombectomy in primary percutaneous intervention for acute myocardial infarction

Abstracts

A intervenção coronariana percutânea (ICP) primária tem se tornado a estratégia favorita para reperfusão em infarto agudo do miocárdio com elevação do segmento ST (STEMI). Um grau mais baixo de perfusão miocárdica pós-ICP, no-reflow e até trombose de stent farmacológico tem sido relacionados à presença de trombo intracoronário. A trombectomia adjunta refere-se a procedimentos e dispositivos que removem o material trombótico da artéria associada ao infarto, em teoria, antes que a embolização distal possa ocorrer. Há significante variabilidade entre estudos controlados randomizados de trombectomia em ICP primária em relação aos dispositivos testados, características dos procedimentos, terapia médica adjuvante e desfechos analisados. Em geral, melhoras nos endpoints de perfusão miocárdica não são traduzidas em reduções nos desfechos clínicos. Ainda assim, um número crescente de estudos com maior tempo de seguimento relatou benefícios tardios após o infarto do miocárdio inicial. Cateteres de aspiração simples também podem produzir melhores desfechos do que dispositivos que fragmentam o trombo antes de aspirar os resíduos. As variáveis clínicas ou angiográficas que melhor predizem os benefícios do uso da trombectomia ainda precisam ser definidas. O objetivo dessa revisão é dar uma perspectiva sobre as conclusões de estudos disponíveis e meta-análises de trombectomia adjunta em infarto agudo do miocárdio. Também são discutidos os objetivos para futuros estudos.

Trombose; trombectomia; angioplastia coronariana com balão; infarto do miocárdio

La intervención coronaria percutánea (ICP) primaria se ha convertido en la estrategia favorita para la reperfusión en el infarto agudo del miocardio con la elevación del segmento ST (STEMI). Un grado más bajo de perfusión miocárdica post- ICP, no-reflow e incluso trombosis de stent farmacológico ha sido relacionado con la presencia de trombo intracoronario. La trombectomía adyuvante se refiere a procedimientos y dispositivos que retiran el material trombótico de la arteria asociada al infarto y en teoría, antes que la embolización distal pueda ocurrir. Existe una significativa variación entre los estudios controlados randomizados de trombectomía en ICP primaria, con relación a los dispositivos testados, características de los procedimientos, terapia médica adyuvante y desenlaces analizados. En general, las mejorías en los endpoints de perfusión miocárdica no se traducen en reducciones en los desenlaces clínicos. Pero incluso así, un gran número de estudios con mayor tiempo de seguimiento indicó que se notan beneficios tardíos después del infarto del miocardio inicial. Los catéteres de aspiración simple también pueden producir mejores desenlaces que los dispositivos que fragmentan el trombo antes de aspirar los residuos. Las variables clínicas o angiográficas que mejor pueden predecir los beneficios del uso de la trombectomía, todavía tienen que ser definidas. El objetivo de esta revisión es ofrecer una perspectiva sobre las conclusiones de estudios existentes y de metanálisis de trombectomía adyuvante en infarto agudo del miocardio. También se discuten aquí los objetivos para futuros estudios.

Trombosis; trombectomía; angioplastia coronaria con balón; infarto del miocardio

CLINICAL UPDATE

^ICardiovascular Division, Brigham and Women's Hospital, Boston MA - USA

^IINoninvasive Cardiology Service, Montreal Heart Institute, Université de Montréal, Montréal QC - Canadá

^IIIFaculdade de Ciências Médicas, Univesidade Estadual de Campinas - UNICAMP, Campinas, SP - Brasil

^IVInstitut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Quebec City - Canadá

Mailing Address

ABSTRACT

Primary percutaneous coronary intervention (PCI) has become the favored reperfusion strategy in acute ST-segment elevation myocardial infarction. Lower post-PCI myocardial perfusion grade, no-reflow and even drug-eluting stent thrombosis have been related to the presence of intracoronary thrombus. Adjunctive thrombectomy refers to procedures and devices that remove thrombotic material from the infarctionrelated artery, in theory, before distal embolization can occur. There is substantial variability between randomized controlled trials of thrombectomy in primary PCI with regards to tested devices, procedural characteristics, adjuvant medical regimen and examined outcomes. As a general statement, improvements in myocardial perfusion endpoints do not translate into reductions in clinical outcomes. Yet, an increasing number of trials with a longer follow-up reported benefits arising late after the index myocardial infarction. Simple aspiration catheters may also produce better outcomes than devices that fragment the thrombus before aspirating debris. Clinical or angiographic variables which best predict benefits from the use of thrombectomy remain to be defined. The aim of this review is to provide perspective on the conclusions of available trials and meta-analysis of adjunctive thrombectomy in acute myocardial infarction. Targets for future studies are discussed.

Keywords: Thrombosis; thrombectomy; angioplasty,balloon,coronary; myocardial infarction.

Introduction

The goal of reperfusion therapy in acute ST segment elevation myocardial infarction (MI) is to achieve patency of the epicardial infarct-related artery and to restore myocardial tissue perfusion. In randomized controlled trials (RCT), primary percutaneous coronary intervention (PCI) leads to lower mortality, less reinfarction and fewer strokes than thrombolysis¹. When readily available, primary PCI has become the favored reperfusion strategy in acute MI. However, suboptimal results in primary PCI, such as lower TIMI (thrombolysis in myocardial infarction) myocardial perfusion grade (TMPG) or myocardial blush grade (MBG), no-reflow and even drug-eluting stent thrombosis have been related to the presence of intracoronary thrombus. Angiography, myocardial contrast echocardiography (MCE) and cardiovascular magnetic resonance (CMR) provide evidence that microvascular obstruction is prevalent after primary PCI^2-4.

Thrombectomy, or mechanically removing thrombus from the coronary artery, may improve prognosis after MI as it can, in theory, prevent distal embolization of thrombus and its dismal consequences. Observational studies have shown favorable outcomes with adjunctive thrombectomy, such as implantation of a stent that is shorter than the original lesion with its thrombus⁵. With flow restoration following thrombectomy, it is often possible to perform direct stenting, without balloon dilatation⁶. Several small to moderate-sized RCTs have been published in the recent years. They yielded inconsistent results on the impact of adjunctive thrombectomy on reperfusion surrogate and clinical endpoints. Therefore, the role of adjunctive thrombectomy in primary PCI is debatable⁷. Operators are left with an armada of devices, high hopes to improve the results of primary PCI, but conflicting data on which to base their practice. The aim of this review is to provide perspective on the conclusions of available RCTs and meta-analysis of adjunctive thrombectomy in acute MI.

Assesment of myocardial reperfusion

The underlying hypothesis for using thrombectomy is that thrombus removal may protect the myocardial microcirculation. Microvascular obstruction appears on imaging studies as myocardium which fails to uptake contrast material⁸. Selected RCTs of adjunctive thrombectomy have used MCE^3,9, Tc-99m sestamibi gated single photon emission computed tomography (SPECT)^10-14 and late gadolinium enhancement by CMR⁴. Yet, most RCTs have relied on validated angiographic or electrocardiographic surrogate markers or myocardial perfusion¹⁵. De Luca et al¹⁵ reported thatTMPG, corrected TIMI frame count (cTFC) and residual cumulative ST segment deviation all showed a linear relationship with peak creatine kinase MB (CK-MB), considered as gold standard for infarction size. Patients with the combined presence of a residual ST segment deviation of 0-2 mm, cTFC < 14 and TMPG 3 had a very small infarction and good post-discharge left ventricular ejection fraction (LVEF). TMPG is an independent predictor of 30-day mortality after MI. There is a stepwise improvement in outcome with better TMPG and it allows further risk stratification than flow evaluation alone¹⁶. There is also a stepwise increase in infarction size by SPECT or CK-MB with lower TMPG¹⁷. ST segment resolution identifies candidates for rescue PCI, is indicative of tissue level perfusion after reperfusion therapy, and is available at the bedside¹⁸. Post-MI mortality, congestive heart failure, infarction size and LVEF are related to the extent of ST segment resolution^17,19. Overall, there is strong evidence to support that if adjunctive thrombectomy can lead to improvements in these surrogate endpoints, clinical benefit would logically follow.

Intracoronary thrombus in PCI

There is good evidence that the presence of thrombus leads to suboptimal results in PCI. Thrombus dislodgment leads to macro or microembolization. Macroembolization, defined as a distal filling defect with an abrupt cutoff in one of the peripheral coronary artery branches of the infarction-related vessel, distal to the site of angioplasty, is reported to occur in 15.2% of primary PCI²⁰. It has been associated with lower TIMI 3 flow, less residual stenosis < 50%, lower MBG, lower ST segment resolution, larger enzymatic infarction size, lower LVEF at discharge, left ventricular remodeling and higher long-term mortality^3,20.

Microembolization results in microvascular dysfunction assessed by MCE in the area at risk after primary PCI. It is associated with left ventricular dilatation at 6 months and is a predictor of cardiac death, reinfarction and heart failure²¹. A large thrombus burden was found to predict the occurrence of adverse cardiovascular events after primary PCI, possibly because the thrombus in the infarction-related artery prevents complete stent apposition and promotes stent thrombosis²². Embolization with subsequent microvascular dysfunction is among the possible mechanisms resulting in absence of epicardial flow despite a reopened artery (no-reflow)⁸.

Yip et al²³ identified thrombus characteristics in the pre-revascularization angiogram, which independently predicted the occurrence of no-reflow in a cohort of patients treated with primary PCI without glycoprotein IIb/IIIa inhibitors and without stenting in their earliest experience²³. In that study, a thrombus length greater than 3 times the lumen diameter and floating or accumulated thrombus proximal to the artery occlusion appeared at higher risk for slow flow or no-reflow²³.

Adjunctive thrombectomy

Adjunctive thrombectomy refers to procedures and devices that remove thrombotic material from the infarction-related artery, in theory, before distal embolization can occur. This review will focus on thrombectomy performed as the first step during emergent PCI for ST elevation MI, immediately after crossing the culprit lesion with a guidewire. Thrombectomy in acute MI has also been tested in combination with a distal protection device destined to capture thrombus fragment that would have escaped aspiration²⁴. The large EMERALD RCT was negative and this strategy has not gained acceptance.

The substantial variability among available thrombectomy devices can make comparison between trials difficult. Devices differ in mechanisms of action, catheter size and performance at thrombus removal. Table 1 lists the devices that have been tested in RCTs. Bavry et al²⁵ have proposed to distinguish between devices that simply aspirate the thrombus from the artery (aspiration thrombectomy) and devices that fragment the thrombus before aspirating the debris (mechanical thrombectomy). Simple, less bulky, aspiration devices have been tested in a larger sample of patients than mechanical thrombectomy devices. The widespread use of aspiration devices has been advocated based on the ATTEMPT pooled analysis^26,27. In another meta-analysis, we did not find a substantial advantage to aspiration thrombectomy²⁸. The recently published and positive JETSTENT trial, which tested the AngioJet rheolytic thrombectomy device in nearly 500 patients, may revive the interest for mechanical thrombectomy¹⁴. A recent study also found that the single or multicenter study design has a significant impact on outcomes in trials examining the efficacy of adjunctive devices in acute MI²⁹.

The cost-effectiveness of adjunctive thrombectomy has been relatively unexplored. Mechanical devices are expected to cost more than simple aspiration catheters. Ideally, the incremental cost should be justified by improved outcomes. Very limited data suggest that thrombectomy does not cost more than standard therapy in the setting of acute MI³⁰. Rheolytic thrombectomy improved clinical outcomes and reduced overall medical care costs in comparison to urokinase in patients with extensive thrombus in vein grafts³¹.

Studies of adjunctive thrombectomy in primary PCI

Inclusion and exclusion criteria

The typical eligibility criterion for RCTs of adjunctive thrombectomy was ST-segment elevation MI referred for primary or rescue PCI within 12 hours of symptoms onset. The maximal time after symptoms onset was 6 hours in one trial³², 9 hours in another⁴, 24 hours in one trial³³and 48 hours in one trial¹³. An angiographically visible thrombus was required in 6 trials (Table 2 and 3)^4,14,34-37. Patients in shock, requiring intra-aortic balloon counterpulsation or mechanical ventilation were excluded from 10 trials^{4,10,11,13,34, 37-41} and patients with previous coronary artery bypass were excluded from 9 trials^{4,12,13,33,34,39-42}. Only 2 RCTs specifically excluded patients with a LVEF below 30%^10,38. Six trials reported crossovers from the control to the thrombectomy group (range 3-18 patients)^{6,10,11,39,41,43}. One trial recruited only anterior MIs³⁴. Some trials required an infarction-related artery minimal reference diameter of at least 2.5 mm^{4,11,14,24,33,35,37,38,41} or 2 mm¹⁰. Patients with left main coronary stenosis were excluded from 6 trials^{4,12,33,35,40,42} and those with excessively calcified and tortuous arteries were excluded from one trial³⁸. Overall, RCTs mostly included low to moderate-risk MI patients without hemodynamic compromise or high risk coronary anatomy.

Randomized controlled trials of aspiration thrombectomy

The majority of aspiration thrombectomy RCTs found a statistically significant improvement in one or a combination of surrogate markers of myocardial reperfusion (Table 2). This finding appears consistent with all available devices. On the contrary, none of the trials found that adjunctive thrombectomy reduced major adverse cardiovascular events (MACE) at a follow-up varying from the hospital stay to 6 months after MI (Table 2). Even in the largest trial (TAPAS), which is the most likely to be adequately powered, no difference in early clinical outcomes was found⁶. The definition of MACE consistently included mortality and nonfatal reinfarction. The select RCTs that extended patient follow-up until 8 to 24 months after MI all reported a lower occurrence of MACE in patients treated with aspiration thrombectomy^4,33,44,45. The mechanism for this late improvement in clinical outcomes is not defined. If one believes that aspiration thrombectomy favors positive ventricular remodeling, it is plausible that benefits only become apparent at late follow-up or when negative remodeling has had time to occur in patients treated with PCI alone.

Data about infarction size in thrombectomy treated patients at more than 6 months after MI are very limited³. Only 2 RCTs were able to demonstrate a reduction in infarction size with thrombectomy^9,11 (Table 4) and among them, one used aspiration thrombectomy. Most RCTs yielded neutral results for that outcome, if they did not find that thrombectomy increased infarction size (Table 4). Thus, it seems unlikely that aspiration thrombectomy improves clinical outcomes by preventing ventricular dysfunction or arrhythmias arising from a large scar area. Little insight can be gained by examining the causes of MACE in RCTs that report a benefit. In the VAMPIRE trial³³, the reduction in MACE is largely due to a reduction in target lesion revascularization with thrombectomy. This supports the hypothesis that thrombus is associated with poorer PCI results at the level of the lesion as suggested by Sianos et al²². The causes of death at 9 months in the EXPIRA trial and at 1 year in the TAPAS trial have not been reported^4,45. The causes of the 6 deaths at 2 years in the PCI alone group of the EXPIRA trial are evenly split between ventricular fibrillation (3), heart failure (2) and reinfarction (1)⁴⁴. To summarize, aspiration thrombectomy improves myocardial perfusion and late clinical outcomes, but this benefit cannot be explained by a reduction in infarction size.

Randomized controlled trials of mechanical thrombectomy

The conclusionsof mechanical thrombectomy RCTs are similar to those of aspiration thrombectomy RCTs (Table 3). The JETSTENT trial¹⁴ stands out as the only one to demonstrate a reduction in MACE at 1 month after MI, which is sustained at 6 months. This finding is remarkable given that the AIMI trial¹⁰, which also used the AngioJet, found poorer myocardial perfusion, increased infarction size and more MACE in patients treated with thrombectomy. Investigators in JETSTENT¹⁴ where careful to use a single pass anterograde technique to avoid diffusion of thrombus fragments in the artery. They also only recruited patients with a substantial thrombus burden after wiring of the infarction-related artery and did not exclude high risk patients (4% of patients in cardiogenic shock). The design and results of JETSTENT¹⁴ raise the question whether adjunctive thrombectomy is best used selectively in higher risk patients with a large thrombus burden. The differences in outcomes between aspiration and mechanical devices may fade with appropriate patient selection.

Meta-analyses and pooled analyses

There is significant heterogeneity in design between individual RCTs, which is an inherent limitation for meta-analyses and pooled analyses. In addition to inclusion and exclusion criteria and tested devices, several procedural variables, such as lesion predilatation, are left to the discretion of the operator. Nevertheless, meta-analyses further confirm that adjunctive thrombectomy leads to improved myocardial perfusion (Table 5). In the meta-analysis by Bavry et al²⁵, the authors were the first to suggest that simple aspiration devices carried a mortality advantage over bulkier mechanical thrombectomy devices, which were found to increase mortality. A similar trend was observed by Tamhane et al⁴⁶. This finding was reinforced by the ATTEMPT pooled analysis²⁶, which found that a mortality benefit was confined to patients treated with manual (aspiration) devices. Another important finding of the ATTEMPT study²⁶ is that thrombectomy improved survival in patients treated with glycoprotein IIb/IIIa inhibitors, suggesting that they should be used routinely in primary PCI, if adjunctive thrombectomy is performed. The strength of the ATTEMPT study is the use of patient level data with an extended follow-up to 1 year²⁶. It is limited by the absence of 6 of 17 eligible RCTs, to which the principal investigators did not grant access to the database²⁶. Mongeon et al²⁸ found that adjunctive thrombectomy may be one of the few preventive measures against no-reflow, but did not find substantially different results with aspiration thrombectomy compared with thrombectomy by any device²⁸. Tamhane et al⁴⁶ observed an increased risk of stroke with thrombectomy. This novel finding is exploratory, but plausible, given the need for more intravascular manipulations to perform thrombectomy. Stroke should be routinely assessed in outcomes of future RCTs or registries of thrombectomy.

Discussion

The improvement in surrogate markers of reperfusion does not translate into clinical benefits

Absence of improvement in short-term clinical outcomes, despite consistent improvements in surrogate markers of myocardial reperfusion with thrombectomy, has been noted in the majority of RCTs (Table 2 and 3). First, the clinical benefits of thrombectomy may arise later after MI and studies with longer follow-up have consistently reported a reduction in 6 to 24-month MACE with thrombectomy (Table 2 and 3). Second, most RCTs had small sample sizes, making them underpowered to detect a difference in clinical outcome, especially in the low to moderate risk MI patients included in trials. The combined incidence of death, MI or stroke at 30 days was below 5% in thrombectomy and PCI alone groups²⁸. Third, most studies excluded patients in cardiogenic shock or with left main coronary artery disease, who may derive a greater benefit from this technique. Fourth, is it possible that the use of thrombectomy induces a delay in reperfusion that offsets any benefit?

Delay to reperfusion

No RCT reported a statistically significant difference in delay to PCI between thrombectomy and control groups (Tables 2 and 3). Different time intervals are reported from trial to trial. On average, symptom onset-to-balloon times are shorter in thrombectomy-treated patients compared with patients undergoing PCI alone, but this difference is not statistically significant²⁸. Benefits in clinical outcomes with thrombectomy cannot be explained by a shorter time to treatment^4,6,14,33,44.

Likewise, delays to PCI were not longer in thrombectomy groups of negative RCTs^10,12. Of note, the door-to-balloon times in the TAPAS trial were very short and may be difficult to reproduce outside a study setting⁶. Overall, current data do not support that thrombectomy induces clinically relevant delays to treatment, acknowledging that thrombus aspiration with simpler devices is more readily available and easier to set up than more complex devices such as the AngioJet. It is possible that thrombectomy has a distinct capacity to remove thrombus that has been formed for fewer hours⁴⁰. In one study, TIMI flow and MBG were better in thrombectomy-treated patients compared with PCI alone only when the symptom onset-to-catheterization laboratory time was between 4 to 8 hours⁴⁰. No significant difference in myocardial perfusion markers was found for patients treated less than 4 hours after symptom onset⁴⁰. Thus, adjunctive thrombectomy may be less relevant in patients presenting very early after symptom onset.

Infarction size

Most trials found no difference in infarction size with thrombectomy (Table 4). Embolization may occur at times when thrombectomy cannot prevent it: prior to arrival to the catheterization laboratory, with contrast injection or with wire or device crossing of the culprit lesion (distal to proximal technique with activation of the device after crossing the lesion¹⁰). Impaired microvascular perfusion may also be related to other mechanisms such as necrosis, edema, reperfusion injury and endothelial dysfunction⁸.

Two trials, one using a mechanical device¹⁰ and one using an aspiration device¹², found larger infarctions in thrombectomy-treated patients. The JETSTENT investigators advocated the single anterograde technique to avoid promoting distal embolization, but no infarction size reduction was found in that trial¹⁴. Antoniucci et al¹¹ found a reduction in infarction size with the AngioJet in a previous trial, but the thrombectomy technique was not detailed. Liistro et al. found better myocardial perfusion by MCE in patients treated with the Export aspiration catheter⁹. Aspiration was started before crossing the lesion and maintained until catheter withdrawal⁹. Comparisons between RCTs must take into account that infarction size measurement is sensitive to the time delay after the index MI and that difference exists between imaging techniques.

The presence of thrombus

Adjunctive thrombectomy is unlikely to be helpful in the absence of intracoronary thrombus and may even be hazardous. A visual semiquantitative method for the assessment of intracoronary thrombus has been described⁴⁷. Because the thrombus is not always visible in the angiography, most RCTs tested a strategy of systematic thrombectomy in primary PCI and thrombus presence in the baseline angiography was an inclusion criterion in only 6 RCTs (Tables 2 and 3)^4,14,34-37. All of them found that thrombectomy improved surrogate markers of myocardial reperfusion and 2 reported a reduction in clinical events^4,14. An alternative way to account for the presence of thrombus is to examine the material retrieved by the thrombectomy device, which was noted in 5 RCTs^{6,33,35,39,41}. All these trials also yielded positive results for their respective primary outcome. Macroscopic debris was retrieved in 72.9% to 95% of patients^6,33,39. The value of the presence of thrombus on angiography to select patients who can benefit from adjunctive thrombectomy is further supported by a subgroup analysis of the REMEDIA trial, which found more post-PCI MBG > 2 and ST segment resolution > 70% in patients with a baseline TIMI thrombus score 3-4⁴⁷ treated with thrombectomy⁴³. Other subgroup analyses, however, yielded opposite results. In the TAPAS trial, there was no significant difference in risk ratio for post-PCI MBG 0-1 with aspiration thrombectomy versus PCI alone, according to the baseline thrombus score⁶. In the AIMI trial, thrombectomy did not reduce infarction size in the subgroup of patients with visible thrombus at baseline¹⁰. In the study by Kaltoft et al¹², infarction size was larger in patients with baseline thrombus, as it was for the whole thrombectomy group.

Anti-platelet therapy

Contemporary management of ST-segment elevation MI involves the use of various antithrombotic agents⁴⁸. Based on the ATTEMPT pooled analysis²⁶, the use of glycoprotein IIb/IIIa inhibitors is associated with a survival benefit in patients treated with adjunctive thrombectomy and these glycoprotein IIb/IIIa inhibitors were used in more than 75% of patients included in adjunctive thrombectomy RCTs²⁸. Practice guidelines rather encourage the use of dual anti-platelet therapy with aspirin and thienopyridine with heparin or bivalirudin⁴⁸. The use of glycoprotein IIb/IIIa inhibitors is not supported as a routine therapy, but in selected cases with a large thrombus burden or without adequate thienopyridine loading dose⁴⁸. Moreover, a loading dose of 600 mg of clopidogrel is often used and dual anti-platelet therapy is continued for 12 months or more after primary PCI⁴⁸. Prasugrel may also be used. Assuming that these recommendations are followed, some patients may undergo thrombectomy with an antithrombotic regimen that is slightly different from the one largely tested. The pre-PCI loading dose of clopidogrel was 300 mg in most trials that reported it^{4,10,12,13,40,42,43} and it was given for one month after PCI when this information was available^{10,11,34,36,43}. Selected RCTs used a 600 mg loading dose^6,9,14 or maintained its use for 3 to 12 months^4,12,40,42. As the adjunctive medical regimen evolves, the outcomes of adjunctive thrombectomy will require reappraisal in RCTs more closely reflecting the contemporary practice. It remains unknown if more potent antithrombotic drugs given at the time of primary PCI will improve or offset the benefits of adjunctive thrombectomy. At least, intracoronary administration of abciximab, even at higher dosage, did not result in benefits over the usual intravenous regimen in one small trial⁴⁹.

Are aspiration devices better than mechanical devices?

Aspiration thrombectomy has gained increasing popularity and acceptance over mechanical thrombectomy based on meta-analyses^25,26, which suggested that aspiration devices were more beneficial as a class. The JETSTENT trial will likely force the reconsideration of the role of mechanical thrombectomy (Table 3)¹⁴. Mongeon et al²⁸ did not find thrombectomy with an aspiration device to yield substantially different results compared to thrombectomy with any device²⁸. Vlaar et al⁵⁰ compared the Diver and Export aspiration devices (Table 1) and found that a larger internal lumen diameter did not result in retrieval of larger thrombotic particles, nor did it improve angiographic or electrocardiographic outcomes⁵⁰. The RETAMI trial found that the Export catheter removed more thrombotic material and was associated with better myocardial perfusion that the Diver device⁵¹. We can at least say that thrombus aspiration is easier to set up, and usually a cheaper strategy that does not rely on an expensive console to work. As a result, it has gained popularity over the recent years.

Recommendations

The fact that adjunctive thrombectomy yielded benefits on myocardial perfusion endpoints and that it is sound to remove the thrombus for the infarction-related artery have led to its enthusiastic acceptance in primary PCI. Upon review of the available RCTs (Tables 2 and 3) and summary studies (Table 5), one can choose arguments either to justify or reject the use of this technique. Aspiration thrombectomy has appeared as the favored technique in recent studies (Tables 2 and ⁴).

What we know

In the more recent trials (Tables 2 and 3), adjunctive thrombectomy, either by aspiration or mechanical device, performed in unselected acute MI patients undergoing primary PCI was not shown to increase adverse events or costs³⁰. Adjunctive thrombectomy consistently improves surrogate markers of myocardial reperfusion and can reduce the occurrence of late MACE. It is probably best to use adjunctive thrombectomy in conjunction with glycoprotein IIb/IIIa inhibitors²⁶ and in patients with an intermediate symptom onset-to-catheterization laboratory time delay⁴⁰.

What we do not know

The body of favorable evidence is much larger with aspiration thrombectomy (Table 2) than with mechanical thrombectomy (Table 3). Until the JETSTENT trial¹⁴, aspiration thrombectomy was the only technique shown to reduce MACE after MI. The superiority of aspiration thrombectomy remains controversial, but its technical simplicity cannot be ignored. It is still unclear if there are patients who should undoubtedly receive thrombectomy. Subgroup analysis and review of RCTs inclusion criteria do not allow us to use the baseline thrombus burden as an indication for adjunctive thrombectomy. The benefits of a routine thrombectomy approach compared with a more selective use of these devices are also unknown. An appropriately powered trial to study clinical outcomes would need a very large number of patients, as differences in clinical event rates between thrombectomy and control arms are below 1% in selected trials²⁸. A large trial with a planned enrolment of 4,000 patients and reporting outcomes at 6 months is being planned⁵². In addition, future trials should focus on high risk patients, routinely assess the presence of thrombus and report long-term outcomes, as clinical benefits appear to arise later.

Practice guidelines

The American College of Cardiology/American Heart Association 2009 update in the management of ST segment elevation MI gives aspiration thrombectomy a class IIa recommendation. The guidelines committee carefully observes that "it is reasonable to assume that [aspiration thrombectomy] can be useful in [ST-elevation MI] patients with short ischemic times and large thrombus burden. It may not be helpful in [ST-elevation MI] patients with long ischemic times, side branches with small infarction territories, or lesions with low thrombus burden"⁴⁸. The European Society of Cardiology guidelines for management of ST-segment elevation MI gave also a class IIa recommendation for manual thrombus aspiration for prevention of no-reflow, but a class IIb recommendation as a reperfusion procedure⁵³. Finally, one must keep in mind that thrombectomy RCTs were carried out in high-volume centers by experienced operators. It is recommended that operators ensure sufficient proficiency in the manipulation of thrombectomy devices to use them during emergency PCI⁵⁴.

Conclusions

Adjunctive thrombectomy in primary PCI for acute ST segment elevation MI improves myocardial reperfusion. Evidence emerges to suggest that this technique may also improve late clinical outcomes. Based on current practice guidelines, experienced operators should consider the use of adjunctive thrombectomy. Whether it should be routinely performed or selectively used in patients at higher risk or with a large thrombus burden remains to be defined.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any post-graduation program.

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Adjunctive thrombectomy in primary percutaneous intervention for acute myocardial infarction

François-Pierre Mongeon^I,II; Otávio Rizzi Coelho-Filho^I; Otávio Rizzi Coelho^III; Stéphane Rinfret^IV

Publication Dates

• Publication in this collection
  30 Nov 2011
• Date of issue
  Oct 2011

History

• Accepted
  20 Dec 2010
• Reviewed
  20 Dec 2010
• Received
  23 Oct 2010