Value of Thrombus Aspiration in Primary PCI
Abstract & Commentary
By Jonathan Abrams, MD, and Andrew Boyle, MBBS, PhD Dr. Abrams is Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque, and Dr. Boyle is Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis, and Dr. Boyle reports no financial relationship relevant to this field of study.
Source: Svilass T, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008;358:557-567.
For many years, treatment of acute MI with ST segment elevation (STEMI) has been fibrinolytic therapy or percutaneous intervention (PCI), with the primary objective to engage patients as soon as possible after the onset of chest pain in efforts to remove or decrease thrombus burden. In spite of many efforts, very little progress has been made to improve the proportion of patients successfully reperfused with preservation of myocardial tissue and/or a decrease in infarct size. Attempts to directly remove the infarct clot itself have been made, but results are inconclusive. The adverse effects of STEMI include, in part, microvascular embolization of plaque or thrombus material downstream from the infarct site, resulting in microvascular obstruction and inadequate or suboptimal reperfusion, both with thrombolytic agents, as well as PCI. This study sought to evaluate the efficacy of direct aspiration of the thrombus mass causing the infarct in an effort to improve myocardial perfusion, as well as the clinical course of the MI. The TAPAS trial is from University Medical Center in Groningen, The Netherlands, is a prospective, randomized, and open study with blinded evaluation of end points.
The primary purpose of the study was to see whether direct aspiration of the STEMI artery, in addition to PCI, would improve myocardial function, decrease LV muscle loss, and improve clinical outcomes. Approximately 1000 patients were enrolled between January 2005 and December 2006. Admission to the study was dependent on ischemic symptoms lasting greater than 30 minutes, with symptom onset less than 12 hours and ST segment elevation in two or more leads. Patients were randomly assigned to undergo thrombus aspiration during PCI or conventional PCI alone. All subjects had a floppy PCI guide wire passed through the target thrombus. In the aspiration cohort, a six-french aspiration catheter was placed in the target coronary segment, resulting in continuous manual aspiration. Balloon dilation was performed before stenting in appropriate patients; intracoronary nitrates were given to maximize epicardial vasodilatation. Only bare metal stents were utilized. Aspirin, heparin, and clopidogrel were administered, as well as a platelet glycoprotein IIb/IIIa inhibitor.
The primary end point of TAPAS was the post procedure myocardial blush grade of 0 or 1 (no perfusion). Secondary end points included TIMI flow grade of 3, complete or no evidence of persistent ST segment deviation, target vessel revascularization, reinfarction, death, and the combination of major adverse events at 30 days. Coronary angiography was performed before and after PCI. Myocardial blush flow grades were assessed as follows: 0 = no myocardial blush; 1 = minimal myocardial blush or contrast density; 2 = moderate myocardial blush or contrast density, but less than that obtained during angiography of a contralateral or ipsilateral non-infarct-related coronary artery; and 3 = normal myocardial blush or contrast density. Twelve lead EKGs were obtained at presentation and 30-60 minutes after PCI, and ST segments were evaluated for the degree of ST segment resolution. ST deviation was assessed by the degree of ST resolution, including complete (> 70%), partial (30-70%), or none (less than 30%). Aspirated material was examined with H and E and immunostaining, with attention to visualization of smooth muscle and macrophage cells. Aspiration was defined as effective, or not by the presence of atherothrombotic material in the aspirate. Thrombi were defined as containing only platelets, having an RBC component, or thrombus with plaque; length of thrombus was also measured. Follow-up at 30 days was obtained. Target vessel revascularization (TVR), with PCI or CABG, was assessed. Major adverse events included death, reinfarction, or TVR.
Results: The TAPAS cohort included 535 PCI-aspiration patients (T-A) and 536 conventional PCI patients. Baseline clinical and angiographic characteristics were similar in the two groups. Myocardial blush grade of 0-1 (the worst outcome) occurred in 17% of the thrombus-aspiration cohort and 26% of the conventional PCI group, with a 35% risk reduction (P < 0.01). EKG analysis demonstrated complete ST segment resolution in 57% of the T-A group vs 44% of the conventional PCI group; 28% risk reduction (P < 0.001). The T-A group had no persistent ST segment elevation in 53% vs 40% in the conventional PCI patients. Finally, in the T-A group, 24% did not develop pathologic Q waves compared to 16% in conventional group; 54% risk reduction (P = 0.001). Overall, pathologic evaluation was performed in 456 patients; 73% showed atherothrombotic material. Clinical outcomes at 30 days: major bleeding less than 5% in both groups; death, 2.1% vs 4.0%, P = 0.07; reinfarction 0.8% vs 1.9%, P = NS; TVR, 4.5% vs 5.8%, 23% risk reduction, P = NS. Major adverse events at 30 days were 6.8% vs 9.4%, risk ratio 28%, P = NS. The risk of death from adverse events were significantly related to the myocardial blush grade, ST segment elevation, and ST segment deviation, confirming association between death and myocardial blush grade.
Svilass and colleagues conclude that manual aspiration "is feasible in a large majority of patients presenting with STEMI," as predicted by the improved blush grades in the aspiration-PCI cohort. In addition, there was better resolution of ST segment elevation and reduced ST segment deviation in the aspiration subjects. Atherothrombotic debris was retrieved in 73% of subjects, of which the main constituent was platelets.
Dr. Abrams' Commentary
The data from this study are reasonably convincing that the aspiration technique utilized for STEMI was beneficial for a variety of end points, including myocardial blush grade, ST segment elevation resolution, and persistent ST deviation (NS or trends only). These are all surrogate end points. Death rates were low, although higher in PCI-only, as were other major adverse cardiac events in the PCI-only subjects, particularly with blush grade 0 or 1. Figure four of the manuscript displays this data in a dramatic fashion. Other attempts have been made to intervene in STEMI with various thrombectomy approaches, most of which have been positive. Issues such as which type of device is best regarding safety and efficacy, timing of the intervention, and patient selection are not completely resolved. The results of this report should stimulate renewed interest in the aspiration technique. It is unclear whether improvements in catheter design would be useful in the future. Clearly more data are needed, although these results are encouraging. There are relatively few patient selection criteria utilized, making this approach feasible for interventional cardiologists to utilize. While degree of myocardial blush and observations of ST segment changes are related to reperfusion, a soft end point, the clinical and death rates appear to track with the status of ST segment resolution and/or the myocardial blush grade. Some interventional cardiologists in the United States are presently using aspiration techniques, and it is likely and desirable that the results of this study will amplify such an approach to STEMI, which in turn will hopefully increase the desirable results of PCI alone in acute STEMI.
Dr. Boyle's Commentary
This study was well-designed, with randomization performed prior to coronary angiography, unlike many previous trials that only performed thrombectomy in cases of angiographically-visible thrombus. The end points are surrogate end points, and the follow-up period is short. However, these end points correlate with death and MACE. One limitation of the study is that the standard care group had higher rates of balloon predilatation before stenting, whereas the thrombectomy group was usually directly stented after thrombus aspiration. This balloon predilatation may have contributed to distal embolization of platelet-rich thrombus and reduced distal perfusion. Some operators advocate direct stenting in the acute MI situation to minimize distal embolization; however, this is not always possible or practical. Svilass et al conclude that a strategy of initial thrombectomy is feasible in most patients with ST elevation MI, and results in improved myocardial perfusion, regardless of whether there is angiographically visible thrombus. This improvement in perfusion is strongly associated with improvement in clinical outcomes.