Rheolytic Thrombectomy in Acute Myocardial Infarction:
The Florence Experience and Objectives of the Multicenter Randomized JE

The Florence-AngioJet Randomized Trial

The Florence-AngioJet randomized trial was the first study that assessed the efficacy of rheolytic thrombectomy before direct infarct artery stent implantation in patients who underwent PCI for AMI.⁴ This study was based on a sample of 100 patients with a first AMI. The endpoints of the study were early ST-segment elevation resolution, corrected thrombolysis in myocardial infarction (TIMI) frame count and infarct size as assessed by technetium-99m sestamibi scintigraphy at 1 month. Thus, the three endpoints explored the effectiveness of myocardial reperfusion by three different ways (electrocardiography, angiography and scintigraphy). All endpoints were reached. Patients randomized to thrombectomy before direct stenting had a higher incidence of early ST-segment elevation resolution (90% vs. 72%, p = 0.022), lower corrected TIMI frame counts (18.2 ± 7.7 vs. 22.5 ± 11.0, p = 0.032) and smaller infarcts (13.0 ± 11.6% vs. 21.2 ± 18.0%, p = 0.010) as compared to patients randomized to direct stenting alone. By multivariate analysis, the only variables related to the early ST-segment resolution were randomization to thrombectomy (OR 3.56, 95% CI 1.11 to 11.42, p = 0.032) and diabetes mellitus (OR 0.24, 95% CI 0.07 to 0.86, p = 0.029). At 1 month, no patient died, had reinfarction or the need for target vessel revascularization (TVR), and the 6-month clinical outcomes were similar in the two arms: the mortality rate was 2% in both groups and no reinfarction occurred, while TVR rate was 1.4% in the stent alone arm and 2.3% in the rheolytic thrombectomy arm (p = 0.270).
Some characteristics of the study design and other figures of the study deserve specific comment. The study tried to avoid the confounding effects of some procedural variables that may affect the effectiveness of reperfusion such as predilation or postdilation after stenting, different types of stents, use or non-use of glycoprotein IIb/IIIa inhibitors. Direct stenting was attempted in all patients and was successfully performed in 84% of patients, while in 16 patients, predilation was performed after direct stenting attempt failure. After stenting, no patient needed further balloon dilation, and only two types of bare tubular stents were used (one with a closed-cell design, and the other one with an open-cell design; the latter was used in target lesions involving a major branch). Nearly all patients received the same anti-thrombotic treatment [all but two patients had abciximab (ReoPro^®, Eli Lilly, Indianapolis, Indiana) treatment], while crossover to thrombectomy occurred in only four patients of the direct stenting alone arm. The AngioJet^® device (Possis Medical Inc., Minneapolis, Minnesota) directly crossed the target lesion in nearly all cases, and only two patients needed predilation with a small balloon before thrombectomy. Early ST-segment resolution and infarct size were assessed in two predefined and narrow temporal windows (30 minutes from the end of the procedure for ST-segment resolution and 1 month for scintigraphy). The study was powered to detect a difference in early ST-segment resolution, but differences in clinical outcome could not be revealed because of the small number of patients and the criteria used for enrollment (patients with a history of previous MI were excluded).

The AiMI Trial

The AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting in Patients Undergoing Primary PCI for Acute Myocardial Infarction (AiMI) trial is a multi-center, randomized trial that compared rheolytic thrombectomy before angioplasty and stenting of the infarct artery in a sample of 480 patients. The results of this study were presented at the Transcatheter Cardiovascular Therapeutics (TCT) session in October 2004 and are not yet published.⁵ The study failed to show any benefit of rheolytic thrombectomy on infarct size. Moreover, at 30 days, there was a significantly higher mortality in the thrombectomy arm as compared to the control arm (4.6% vs. 0.8%, p = 0.02). Several concerns in study design and in rheolytic thrombectomy technique have suggested the opportunity to perform another study with a different design that overcomes the confounding effect of several procedural variables (predilation, postdilation or direct stenting at the discretion of the operator, thrombectomy performed with a retrograde technique). The thrombectomy technique deserves a specific comment. The relatively high profile of the rheolytic thrombectomy catheter may produce embolism while crossing the lesion without activation. Thus, the retrograde technique often used in the AiMI trial could, in part, explain the negative result of the study.

The JETSTENT Trial

The AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction (JETSTENT) trial is a multi-center, international randomized trial that will compare rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute MI. There are some differences in study design as compared to the Florence trial design. In order to enroll a real-world AMI population, patients with a history of previous myocardial infarction will be enrolled. No restriction based on clinical status on presentation or high-risk coronary anatomy will be used. Thus, patients with cardiogenic shock will be included. Unlike the AiMI study, all JETSTENT patients must have angiographically visible thrombus, or a total occlusion persisting after wiring. Thrombectomy will be performed using an antegrade technique (the first rheolytic thrombectomy pass is made using a proximal-to-distal approach). The two co-primary endpoints of the study are ST-segment resolution at 30 to 45 minutes post-PCI, assessed by 12-lead electrocardiogram (ECG) and infarct size as measured by technetium Tc 99m sestamibi imaging at 30 days. Key secondary endpoints are: 6-month and 12-month mortality and hospital admission for congestive heart failure.
The primary hypothesis of the study is that rheolytic thrombectomy before infarct artery stenting provides a better reperfusion as assessed by ST-segment elevation resolution and/or scintigraphic infarct size. The subsequent increase in myocardial salvage could result in a decreased incidence of death and congestive heart failure due to left ventricle (LV) remodeling at a mid-term follow up.
The ST-segment changes will be evaluated in the single electrocardiographic lead with the most prominent ST-segment elevation before mechanical intervention. The ST-segment elevation is measured to the nearest 0.5 mm at 60 ms after the J point. ST-segment elevation resolution is defined as a reduction in ST-segment elevation ≥ 50% at 30 to 45 minutes after the end of the procedure. This method of ECG analysis deserves a comment. ST-segment elevation resolution is strongly related to outcome after fibrinolytic treatment and has been extensively studied in fibrinolytic trials. Conversely, there are few studies on ST-segment changes after primary PCI, and the most accurate method of assessment of ST-segment changes after primary PCI has not been firmly established. ST-segment resolution was categorized by the investigators of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial as none (< 30%), partial (30 to 70%) and complete (> 70%) within 4 hours of the procedure.^9,10 Complete ST-segment resolution was independently related to mortality and reinfarction at 12 months and 1 year. The same investigators showed the superiority of ST-segment resolution as compared to blush grade in predicting death and reinfarction. They also compared different methods for the assessment of ST-segment resolution after primary PCI. Maximum ST-segment resolution in the single lead with maximum baseline ST-segment elevation was equivalent to the summed % ST-segment resolution across multiple leads, suggesting that the simple method based on the single lead with the most prominent ST-segment elevation should be preferred.
However, several points of this study should be noted: (1) One-third of patients were excluded from the analysis and the exclusion was due to missing data or technical reasons (artifacts, pacing, left bundle branch block, arrhythmias, ST-segment resolution before PCI); 2) ECGs were not registered at definite times, but a large temporal window was used; (3) The use of a broad range of ST-segment resolution, 30 to 70%, resulted in the inclusion of many patients in the category of partial resolution, decreasing the predictive accuracy of ST-segment resolution < 70%. In the JETSTENT trial, early ST-segment resolution is defined as ST segment resolution > 50% at 30 to 45 minutes from PCI. This method was validated by myocardial contrast echography and overcomes the limitations in the use of the large “gray” category of patients with ST segment resolution > 30% and < 70% after PCI.¹¹
The sample size of the JETSTENT trial will be 500 patients and is calculated on the statistical hypothesis of a 30% reduction in infarct size in patients randomized to thrombectomy (power 90%). The study started in January 2006, and the end of enrollment is planned for December 2006.

References

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