This symposium has sought to understand and resolve some of the disparate results from studies evaluating thrombectomy with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) and has attempted to provide a rational approach for current management of patients treated with primary PCI who have large thrombus burden. Most of the randomized trials evaluating adjunctive thrombectomy with primary PCI have enrolled small numbers of patients, and all of the trials have used surrogate endpoints — usually measures of myocardial reperfusion (such as ST-segment resolution and angiographic myocardial blush) or infarct size. Four randomized trials with aspiration thrombectomy have yielded conflicting results — three showing improved myocardial reperfusion with thrombectomy and one showing larger infarct size with thrombectomy. One small randomized trial evaluating Rheolytic™ thrombectomy with primary PCI showed improved myocardial reperfusion and smaller infarct size with the AngioJet® (Possis Medical Inc., Minneapolis, Minnesota), but the large, multi-center, randomized AngioJet in acute Myocardial Infarction (AiMI) Trial found no improvement in myocardial reperfusion, and infarct size was slightly larger in patients treated with AngioJet. The AiMI trial also raised safety concerns because of the higher mortality seen in patients treated with rheolytic thrombectomy.
Data from randomized trials have provided important comparisons between primary PCI with adjunctive thrombectomy and primary PCI alone. However, randomized trials select patients with well-defined, predetermined entry criteria and the results from these trials may not provide a full perspective on the role of thrombectomy in a broad STEMI patient population. The Registries presented in this symposium provide important observational data regarding the use of AngioJet in “real world” STEMI patients with large thrombus burden treated with primary PCI by experienced operators.
Dr. Sianos and colleagues from the Thoraxcenter in Rotterdam, The Netherlands, evaluated outcomes in patients with large thrombus burden treated with primary PCI with and without rheolytic thrombectomy. Patients treated with thrombectomy (n = 75) had better resolution of thrombus, better thrombosis in myocardial infarction (TIMI) flow post-PCI, better myocardial blush post-PCI and better major adverse cardiac events (MACE)-free survival out to 2 years.
Dr. Sharma and colleagues at Mount Sinai Hospital in New York City evaluated data in patients with STEMI and large thrombus burden and compared outcomes in patients treated with primary PCI and adjunctive rheolytic thrombectomy (n = 52) with patients treated with primary PCI alone. Patients treated with the AngioJet had better TIMI flow and better myocardial blush post-PCI and had better event-free survival at 1 year.
Dr. Matthews and colleagues (Sherev, et al.) at the Good Samaritan Hospital in Los Angeles evaluated rheolytic thrombectomy with rescue PCI for failed thrombolysis, a subset of patients with large thrombus burden in the infarct artery and increased risk for clinical events. Patients treated with thrombectomy (n = 32) compared with matched controls treated with rescue PCI alone had more effective resolution of thrombus, less no re-flow, trends toward better procedural success and significantly better clinical success (procedural success free of MACE).
Dr. Dixon and colleagues (Chinnaiyan, et al) at Beaumont Hospital in Royal Oak, Michigan presented one of the largest experiences with the use of the AngioJet with STEMI (n = 239) and found a slightly lower incidence of MACE in patients treated with the AngioJet compared with patients who were treated with primary PCI alone, despite the fact that patients treated with the AngioJet had a higher baseline risk profile. Finally, Dr. Simonton, from the STENT Group, compared outcomes in patients with large thrombus burden treated with AngioJet versus no thrombectomy. Despite having a higher-risk profile, patients treated with AngioJet had a slightly lower mortality. The results of these registries indicate that the use of the AngioJet with primary PCI is safe and suggest that the AngioJet may improve procedural and clinical outcomes in a broad spectrum of real-world STEMI patients treated with primary PCI. While such observational data have limitations and the potential for selection bias, patients are generally selected for treatment with thrombectomy because of large thrombus burden, and such patients are known to be at increased risk for adverse procedural and post-procedural events. Therefore, any selection bias would likely favor better outcomes in non-AngioJet patients.
How do the results of these registries help us to put the results of the AiMI trial in perspective? In the AiMI trial, the mortality and MACE rates were higher with rheolytic thrombectomy than with the control. The study was not powered to detect differences in clinical events, so the findings were quite surprising. The differences in mortality were not due to a high mortality in the AngioJet arm, but rather to an unexpectedly low mortality in the control arm (0.8%, lower than any previously reported primary PCI trial). The data and safety monitoring committee reviewed the deaths in the trial and did not find that any of the deaths were directly attributed to device use. Based on these considerations and the results of the five registries described above, all of which found equivalent or lower mortality and MACE rates with AngioJet, it does not appear that safety is an issue with the AngioJet.
But why did the AiMI trial find no improvement in myocardial perfusion and no reduction in infarct size with rheolytic thrombectomy? There are several possible explanations. There were differences in baseline TIMI flow (better in the control group), which could have influenced outcomes in favor of the control group. Operator technique could be a factor. It is now felt that activating the AngioJet starting with initial antegrade crossing is the appropriate technique for minimizing distal embolization. This was not done systematically in the AiMI trial. It is possible that thrombectomy may be beneficial in the subgroup of patients with large thrombus burden, but these patients comprised a small proportion of patients in AiMI and any benefit may have been lost when outcomes were examined for all patients. The AngioJet is the most effective device for removing thrombus, but it is possible that the device may contribute to distal embolization, which could result in increased infarct size. Finally, distal embolization may not be the major cause for impaired microvascular reperfusion. Other factors, such as reperfusion injury or delayed reperfusion with irreversible damage to the microvasculature, may be the major factors in impaired myocardial reperfusion.
Some of the answers to the questions raised by the results of the AiMI trial may come from the AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction (JETSTENT) trial, which is ongoing and which was discussed by Dr. Antoniucci in this symposium. This trial will randomize 500 STEMI patients treated with primary PCI to AngioJet versus control. Only patients with large thrombus burden will be included and antegrade activation of the device will be mandated by protocol. In addition, pre-dilation is strongly discouraged. The results of this trial should overcome some of the limitations of AiMI and should help answer the question whether AngioJet is effective in improving outcomes in STEMI patients with large thrombus burden. Regardless of the results of JETSTENT, further research is needed to improve current devices and to develop new devices that will optimize thrombus removal and minimize or eliminate distal embolization.
Pending the results of JETSTENT, the interventionalist currently is faced with the decision of how to manage STEMI patients with large thrombus burden. We know that patients with large thrombus burden are at increased risk for distal embolization and poor procedural and clinical outcomes. We also know that current devices, especially AngioJet, are effective at removing thrombus. Until further data are available, it seems that the most reasonable strategy is to perform AngioJet thrombectomy in patients with large thrombus burden prior to primary PCI.