Infuse–Acute Myocardial Infarction - INFUSE-AMI

Description:

The INFUSE-AMI trial sought to study if intracoronary abciximab and manual aspiration thrombectomy would be associated with superior outcomes in patients presenting with anterior ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI) with bivalirudin.

Hypothesis:

Intracoronary abciximab and manual aspiration thrombectomy would both be associated with a reduction in infarct size in patients presenting with anterior STEMI who underwent PPCI with bivalirudin, as compared with no abciximab and no aspiration thrombectomy, respectively.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Factorial

Patient Populations:

  • Age >18 years
  • STEMI symptoms >30 minutes, with anticipated symptom onset to device time ≤5 hours
  • Infarct artery located in the proximal or mid LAD coronary artery, with TIMI 0/1/2 flow at the time of initial diagnostic angiography (prior to wire passage)
  • Based on coronary anatomy, PCI is indicated for revascularization
  • Only one epicardial coronary artery will be treated
  • Expected ability to deliver a ClearWay™ RX Infusion Catheter to the infarct lesion (absence of excessive tortuosity, diffuse disease or moderate/heavy calcification)

    Number of screened applicants: 6,318
    Number of enrollees: 452
    Duration of follow-up: 30 days
    Mean patient age: 60 years
    Percentage female: 73%
    Ejection fraction: 40%

Exclusions:

  • Prior MI, or known prior systolic dysfunction (known ejection fraction <40% by any prior measure or regional wall motion abnormalities)
  • An elective surgical procedure is planned that would necessitate interruption of antiplatelet agents during the first 12 months post-enrollment
  • Subjects who previously underwent coronary stent implantation and in whom coronary angiography demonstrates stent thrombosis to be the cause of the acute MI
  • Subject has previously undergone an angioplasty or stenting procedure in the LAD artery
  • Definite planned use of aspiration, atherectomy, thrombectomy, and/or distal protection catheters prior to PTCA or stent implantation (other than in subjects randomized to thrombus aspiration)
  • Any contraindication to undergo MRI
  • Multivessel intervention required during the index procedure
  • Severe vessel tortuosity, diffuse disease, or severe calcification is present, which may impede successful delivery of the ClearWay™ RX Infusion Catheter or the Export® Aspiration Catheter
  • Features are present, which are highly unfavorable for PCI
  • Target lesion is present within a bypass graft conduit
  • MI is due to thrombosis within or adjacent to a previously implanted stent
  • Left ventriculography demonstrates severe mitral regurgitation or a ventricular septal defect
  • Unprotected left main stenosis >40% or that will require intervention

Primary Endpoints:

  • Infarct size (percentage of total left ventricular mass) at 30 days

Secondary Endpoints:

  • MACCE (death/MI/stroke/clinically driven target vessel revascularization) at 30 days

Drug/Procedures Used:

Patients undergoing PPCI for anterior STEMI and proximal or mid left anterior descending (LAD) occlusion were randomized in a 2 x 2 fashion to receive either intracoronary abciximab versus no abciximab, and manual aspiration thrombectomy versus thrombectomy. Manual thrombus aspiration was performed with a 6 F Export Catheter (Medtronic). To ensure high intrathrombus drug concentrations, a 0.25 mg/kg bolus of abciximab was administered locally at the site of the infarct lesion via the ClearWay RX Local Therapeutic Infusion Catheter, a microporous “weeping” PTFE balloon mounted on a 2.7F rapid exchange catheter (Atrium Medical). An abciximab infusion after PCI was allowed only for refractory intraprocedural thrombotic complications.

Concomitant Medications:

All patients were administered aspirin, 324 mg orally or 250-500 mg intravenously, and clopidogrel, 600 mg, or prasugrel, 60 mg, after which emergent coronary arteriography and left ventriculography were performed. Patients undergoing PCI received procedural anticoagulation with bivalirudin (intravenous bolus 0.75 mg/kg plus infusion of 1.75 mg/kg/h, discontinued at procedure end) without routine glycoprotein IIb/IIIa inhibition. Unfractionated heparin was used in 64% of the patients prior to diagnostic catheterization.

Principal Findings:

A total of 452 patients were randomized, 229 to aspiration thrombectomy and 223 to no aspiration thrombectomy, and 229 to intracoronary abciximab, and 223 to no abciximab. Baseline characteristics were fairly similar. About 13% had a history of diabetes mellitus, and 2% had undergone prior PCI. The majority of patients had Killip class I congestive heart failure (CHF) on presentation. The median door-to-balloon time was about 45 minutes. The culprit lesion was the proximal LAD in 64% of the patients. TIMI (Thrombolysis in Myocardial Infarction) flow was 0 or 1 in 73% of the patients.

Intracoronary abciximab versus none: There was no difference in the % of patients with TIMI 3 flow post-PCI (91.3% vs. 91.5%, p = 0.94). Complete resolution (>70% resolution of ST-segment resolution) was also similar (50.0% vs. 57.8%, p = 0.13). The primary outcome of infarct size at 30 days, as assessed by cardiac magnetic resonance imaging (MRI) was significantly lower in the abciximab arm, as compared with the no abciximab arm (15.1 vs. 17.9, p = 0.03). Total infarct mass on MRI was lower in the abciximab arm (18.7 g vs. 24.0 g, p = 0.03). All clinical endpoints including major adverse cardiac events (MACE) (7.0% vs. 6.8%, p = 0.91), death (3.5% vs. 2.3%, p = 0.42), reinfarction (0.5% vs. 0.9%, p = 0.56), stent thrombosis (0.9% vs. 0.9%, p = 0.99), and TIMI major bleeding (2.2% vs. 0.5%, p = 0.11) were similar between the two arms.

Manual aspiration thrombectomy versus none: There was no difference in the % of patients with TIMI 3 flow post-PCI (92.6% vs. 90.1%, p = 0.36). Complete resolution (>70% resolution of ST-segment resolution) was also similar (50.8% vs. 56.8%, p = 0.23). The primary outcome of infarct size at 30 days, as assessed by cardiac MRI, was similar between the two arms (17.0 vs. 17.3, p = 0.51). Total infarct mass on MRI was also similar (20.3 g vs. 21.0 g, p = 0.36). All clinical endpoints including MACE (6.6% vs. 7.2%, p = 0.81), death (3.1% vs. 2.7%, p = 0.81), reinfarction (0.5% vs. 0.9%, p = 0.55), stent thrombosis (1.4% vs. 0.5%, p = 0.33), and TIMI major bleeding (1.3% vs. 2.8%, p = 0.30) were similar between the two arms.

No interaction was present between the two randomization groups for the 30-day infarct size endpoint (p = 0.46), although in a subgroup analysis, median infarct size was lowest in the intracoronary abciximab plus aspiration group compared with the other three groups combined.

Interpretation:

The results of this trial indicate that in patients undergoing PPCI for anterior STEMI and receiving bivalirudin: 1) intracoronary abciximab is superior to no abciximab, and 2) manual aspiration thrombectomy is not superior to no thrombectomy, in reducing infarct size at 30 days. Clinical outcomes were similar between the groups, although the trial was not powered to study these differences.

These results are contrary to two of the largest trials on these respective topics. The TAPAS trial demonstrated an unequivocal mortality benefit at 1 year with manual aspiration thrombectomy in patients with STEMI undergoing PPCI. Similarly, the AIDA-STEMI trial demonstrated no clinical benefit with intracoronary abciximab (vs. intravenous abciximab) in these patients. Reasons for these differences are unclear. It is unclear how many patients underwent direct stenting after mechanical thrombectomy in this trial, since that seemed to be clearly beneficial in earlier trials. As far as abciximab is concerned, it is possible that distal delivery of abciximab with a microcatheter (as done in this trial but not in AIDA-STEMI) achieves better local glycoprotein IIb/IIIa inhibition, thereby improving infarct size. Further validation of these findings is necessary.

References:

Stone GW, Maehara A, Witzenbichler B, et al., on behalf of the INFUSE-AMI Investigators. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA 2012;307:1817-1826.

Presented by Dr. Gregg Stone at ACC.12 & ACC-i2 with TCT, Chicago, IL, March 24, 2012.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Imaging, Magnetic Resonance Imaging

Keywords: Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Immunoglobulin Fab Fragments, Magnetic Resonance Imaging, Angioplasty, Balloon, Coronary, Hirudins, Stents, Percutaneous Coronary Intervention, Polytetrafluoroethylene, Thrombectomy, Thrombosis, Heart Failure, Peptide Fragments, Recombinant Proteins, Diabetes Mellitus


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