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The Randomized Leipzig Immediate Percutaneous Coronary Intervention Abciximab IV Versus IC in ST-Elevation Myocardial Infarction Trial - Randomized Leipzig Immediate PCI Abciximab IV vs. IC in STEMI Trial
Description:
The goal of the trial was to evaluate treatment with intravenous (IV) compared with intracoronary (IC) abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).
Hypothesis:
IC abciximab will be more effective in reducing infarct size and extent of microvascular obstruction.
Study Design
- Randomized
Patients Enrolled: 154
Mean Follow Up: 30 days
Mean Patient Age: 65 (range 54-73)
Female: 39
Patient Populations:
Patients with STEMI within 12 hours of symptom onset
Exclusions:
• Prior fibrinolysis
• Allergy to aspirin, heparin, or abciximab
• Active bleeding
• Pregnancy
• Major surgery within the last month
• Cardiogenic shock with mechanical ventilation
• Contraindication to magnetic resonance imaging such as an implanted pacemaker or defibrillator
Primary Endpoints:
Infarct size and extent of microvascular obstruction assessed by magnetic resonance imaging
Secondary Endpoints:
• ST-segment resolution after PCI
• TIMI flow and perfusion grades after PCI
• Infarct size assessed by area under the creatine kinase curve
• MACE defined as death, reinfarction, urgent target vessel revascularization, or new-onset congestive heart failure within 30 days
Drug/Procedures Used:
Patients with STEMI undergoing PCI were randomized to IC abciximab (n = 77) or IV abciximab (n = 77) followed by a 12-hour infusion.
Concomitant Medications:
By protocol, all patients received an abciximab bolus (0.25 mg/kg) prior to PCI followed by a 12-hour infusion (0.125 µg/kg/min). In the IC group, the abciximab bolus was administered after the wire crossed the lesion, although before balloon dilatation. Patients also received aspirin (500 mg), clopidogrel (600 mg), and unfractionated heparin (60 U/kg body weight). Heparin was discontinued for 4 hours after PCI and then reinitiated for a minimum of 12 hours to achieve an activated partial thromboplastin time of 50-75 seconds.
Postprocedure, aspirin was given indefinitely (at least 100 mg daily) and clopidogrel was given for 9 months (75 mg daily).
Principal Findings:
The median time from symptom onset to PCI was 244 minutes in the IC group and 218 minutes in the IV group (p = 0.47). Door-to-balloon time was 31 minutes versus 29 minutes (p = 0.77), respectively. All patients received the abciximab bolus, which was given prior to PCI in 83% of the IC group and 77% of the IV group (p = 0.42). There were no adverse events noted during the administration of IC abciximab. Abciximab infusion was discontinued due to bleeding complications in four of the IC patients versus five of the IV patients (p = 0.93).
The primary outcome, infarct size detected by magnetic resonance imaging, was 15.1% in the IC group and 23.4% in the IV group (p = 0.01). Early microvascular obstruction detected by magnetic resonance imaging was 1.1% versus 3.4% (p = 0.01), whereas late microvascular obstruction was 0.1% versus 1.1% (p = 0.02), respectively for IC versus IV abciximab.
The area under the creatine kinase release curve was 575 µmol/L/h versus 736 µmol/L/h (p = 0.007), ST-segment resolution occurred in 77.8% versus 70.0% (p = 0.006), Thrombolysis in Myocardial Infarction (TIMI) flow grade of 3 after PCI occurred in 84.4% versus 85.7% (p = 0.91), TIMI perfusion grade of 3 after PCI occurred in 72.7% versus 66.2% (p = 0.09), and major adverse cardiac events (MACE) occurred in 5.2% versus 15.6% (p = 0.06), respectively for IC versus IV abciximab.
Interpretation:
Among STEMI patients undergoing PCI, the use of IC abciximab was superior to IV abciximab. IC abciximab bolus followed by 12-hour infusion was associated with significantly smaller infarct size, early and late microvascular obstruction, and ST-segment resolution. IC abciximab also resulted in a nonsignificant reduction in MACE.
Upstream administration of glycoprotein IIb/IIIa inhibitors (i.e., facilitated PCI) has been advocated as a way to achieve superior pre-PCI TIMI flow; however, this approach does not reduce major adverse clinical events (Keeley et al., Lancet 2006;367:579-88). IC abciximab is being studied as a means to improve myocardial perfusion.
Before adapting this strategy into clinical practice, several unique aspects of the trial design should be highlighted. IC abciximab was given after the wire crossed the lesion, although before balloon dilatation. The second point is that heparin was infused for 12 hours after PCI, which is an uncommon practice. The third consideration was the short door-to-balloon times, which may make the results less applicable to centers that are not able to achieve such rapid mechanical reperfusion. The fourth point is that bleeding (i.e., major and minor) was not well characterized. Fifth, the investigators were not blinded to treatment assignment, thus leaving the potential for bias. The last consideration is that while this approach appears promising, an adequately powered trial needs to assess the effect on clinical outcomes.
References:
Thiele H, Schindler K, Friedenberger J, et al. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. The randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation 2008;118:49-57.
Keywords: Myocardial Infarction, Creatine Kinase, Platelet Aggregation Inhibitors, Research Personnel, Dilatation, Heparin, Immunoglobulin Fab Fragments, Magnetic Resonance Imaging, Percutaneous Coronary Intervention
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