Abciximab in AMI:- Is Intra-coronary the way forward?26 April 2012
By: Daniel Jones
2 recently published studies have being assessing the use of abciximab in acute myocardial infarction. Abciximab (a Glycoprotein IIb/IIIa anatagonist) is used routinely in primary percutaneous coronary intervention (PPCI) as recommended by current US and European guidelines. However there are certain issues outstanding with regard to its use as a consequence of previous conflicting results. The effect on infarct size has been debated as had the timing of the administration. INFUSE-AMI was designed to assess the effect of intra-coronary abciximab (and thrombectomy) on infarct size in STEMI with the placebo controlled double-dummy MISTRAL trial designed to assess the timing of the intravenous GPIIb/IIIa administration.
INFUSE-AMI study is a 2x2 factorial, randomized, multicenter, single-blind study of a single 0.25-mg/kg bolus of intracoronary abciximab administered at the site of the infarct lesion vs no abciximab and manual aspiration thrombectomy vs no thrombectomy. Over a two-year period, 452 patients from 37 sites in six countries presenting within four hours of symptom onset with large anterior ST-segment elevation MI (STEMI) due to a proximal or mid-left anterior descending artery occlusion were included in the study. All patients underwent PCI and received procedural anticoagulation with bivalirudin
The intracoronary administration of abciximab delivered to the infarct lesion site resulted in a significant, albeit modest, reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03) and absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). In comparison the use of aspiration thrombectomy failed to have any demonstrable effect on 30 day or absolute myocardial infarct size. At 30 days, neither intracoronary abciximab nor thrombectomy improved myocardial reperfusion, ST-segment resolution, or 30-day clinical event rates.
Although infarct size at 30 days was reduced with intracoronary abciximab, early markers of microcirculatory reperfusion (Myocardial Blush Grade (MBG) and ST-segment resolution (STR)) were not improved, results that are consistent with the comparable 30-day clinical event rates between the groups. Moreover, the magnitude of the absolute reduction in infarct size with intracoronary abciximab, while statistically significant, was modest (mean reduction, 2.3%; 95% CI, 0.2-4.4%, of total left ventricular mass, less than the 6% which was considered clinically relevant during planning of the study). As a result, the increase in left ventricular ejection fraction noted in abciximab-treated patients compared with those not receiving abciximab did not reach statistical significance. Further large scale study is needed to confirm these beneficial effects before intra-coronary is adopted as 1st choice.
The lack of effect on infarct size with thrombectomy in INFUSE-AMI contrasts with the positive one-year results from the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) study. This study showed that aspiration reduced mortality, however they also did not observe a reduction in infarct size at 30 days. There are other ongoing clinical trials (TOTAL and TASTE) that are also studying the safety and efficacy of manual aspiration thrombectomy in patients with STEMI.
MISTRAL Study:- Early abciximab in STEMI
The results of the MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) study demonstrate that early, in-ambulance administration of abciximab did not improve outcomes in STEMI. This was a prospective, randomized, double-blind study involving two hundred and fifty-six patients with acute STEMI of < 6h duration recruited at 11 hospitals in France. The patients were allocated to receive 0.25 mg/kg abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). All patients received aspirin and unfractionated heparin in the ambulance.
The primary end point was complete (>70%) ST-segment resolution (STR) 60 minutes after PCI, for which no difference was seen between the treatment groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Although preprocedural TIMI flow grade 2-3 was numerically more common (46.8% versus 35%, P=0.08) and slow flow (5.6% versus 13.4%, P=0.07 during PCI less frequent among patients who received early rather than late abciximab these differences were not significant. The incidence of procedural embolization was however statistically lower in the early than in the late abciximab group (8.1% vs 21.1%, p=0.008). Infarct size and biomarker levels were similar in both groups during the index hospitalization. The rates of major adverse cardiac events including death, MI, and TVR were equivalent at 11% in each group while major bleeding occurred in 0.8% of the ambulance group and 1.6% of the hospital group.
Despite the largely negative results, the authors concluded that abciximab given very early in the course of STEMI might facilitate primary PCI by improving the visibility of the coronary anatomy, thus allowing a faster and more-accurate procedure. The negative results were consistent with other previous studies such as the FINESSE trial, published in the New England Journal of Medicine in 2008. This study found that early abciximab added to primary PCI did not improve 90-day clinical outcomes over what could be achieved by giving the drug in the cath lab.
Overall these studies have provided further important information about the use of abciximab in PPCI. Administration in the ambulance appears to have limited benefit especially if transfer to the catheterisation lab is efficiently achieved. In contrast intracoronary use appears to reduce infarct size but not effect early outcome. Information on long-term outcome is awaited and may further support routine intra-coronary administration in PPCI patients.
1. Stone GW, Machara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction. JAMA 2012; DOI: 10.1001/jama.2012.421
2. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet. 2008;371(9628):19151920.
3. Ohlmann P, Reydel P, Jacquemin L, et al. Prehospital abciximab in ST-segment elevation myocardial infarction: Results of the randomized, double-blind MISTRAL study. Circ Cardiovasc Interv. 2012;5:69-76.
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