Randomized Early versus Late Abciximab in Acute Myocardial Infarction Treated With Primary Coronary Intervention (RELAx-AMI Trial) Mauro Maioli, MD, Francesco Bellandi, MD, Mario Leoncini, MD, Anna Toso, MD, Roberto Piero Dabizzi, MD Journal of the American College of Cardiology Vol. 49, No. 14, 2007

BACKGROUND

  Glycoprotein IIb/IIIa inhibitior (abciximab) in acute STEMI treated with primary percutaneous coronary intervention (PCI)   improving clinical and angiographic outcome by increasing myocardial reperfusion   significant reduction in 30-day re-infarction   decreased short & long-term mortality → Class IIa recommendation   Early administration of abciximab in STEMI, before arrival in the catheterization laboratory   improve coronary patency   superior pre-PCI Thrombolysis In Myocardial Infarction (TIMI) flow grade 3

  However, optimal timing of administration & impact on myocardial perfusion : not yet well established Evaluate the impact on angiographic outcome left ventricular (LV) function parameters administered in the emergency room compared with in the catheterization laboratory

METHODS

  First AMI candidates for primary PCI   presenting within 12 hrs of symptom onset   ST-segment elevation of more than 1mmin at least 2 contiguous leads   From June 2003 to March 2006 : 210 pts enrolled   Patients received abciximab (0.25 mg/kg as a bolus followed by a 12-h infusion of ug/kg/min) either in the emergency room (early group) or in the catheterization laboratory after diagnostic angiography just before PCI (late group)   All patients received heparin as a bolus of 70 U/kg (maximum 7,000 U) together with 250 mg of aspirin intravenously in the emergency room   Immediately after the procedure, all patients received clopidogrel 300 mg   After PCI, a 24-h infusion of 7 U/kg/h of heparin → The target aPTT time : between 1.5 and 2.0 times the control value   Patients were routinely treated with aspirin (100 mg/day indefinitely) and clopidogrel (75 mg/day for at least 1 month) Population and Trial protocol

  12-lead EKG recorded at presentation, immediately before PCI, and continuously 180 min after coronary artery recanalization   ST-segment resolution (before and within 60 min after PCI) : the ratio between pre-intervention or post-intervention values and initial sum of ST-segment elevation   Complete ST-segment resolution : ≥70% decrease in ST-segment elevation 60 min after recanalization of the IRA   Left ventricular ejection fraction (EF) assessment : echocardiography according to Simpson in classical 2-and 4-chamber apical projections, at arrival in the emergency room and at 1-month follow-up   Wall motion score : 1 through 5 according to a 16-segment model   Wall motion score index (WMSI) : sum of segmental score divided by the number of visualized segments Trial protocol & Definition 1 : normal 2 : hypokinesia 3 : akinesia 4 : dyskinesia 5 : aneurysmal change

  Primary End Point : pre-interventional angiographic finding   TIMI flow grade   cTFC (corrected Thrombolysis In Myocardial Infarction frame count)   MBG (myocardial blush grade)   Secondary End Points   infarct size (measured by cumulative release of serum cardiac markers)   LV functional recovery at 1 month (echocardiographic EF and WMSI) End points Grade 0 : complete occlusion Grade 1 : some penetration without distal coronary a. Grade 2 : distal bed 까지 perfusion 되나 delayed flow Grade 3 : full perfusion

RESULTS

Pre-PCI analysis Post-PCI analysis

DISCUSSION

  In first AMI pts treated with PCI, early abciximab administration in the emergency room compared with late in the catheterization laboratory → significantly improves   Preprocedural angiographic epicardial flow ( by TIMI flow grade)   Tissue perfusion (MBG 2 or 3)   Postinterventional parameters of myocardial reperfusion (MBG ≥2 and ST- segment resolution)   smaller infarct size (cumulative release of serum cardiac markers)   improved LV function at 1-month follow-up (EF and WMSI)   Large randomized trials demonstrated the benefit of abciximab in AMI : improve blood flow both at the epicardial and at the microcirculatory level   Adjunctive abciximab is associated with a significant reduction of 30-day reinfarction and long-term (6 to 12 months) mortality (4.4% vs. 6.2%, p = 0.01) without an increased risk of intracranial bleeding De Luca G, Suryapranata H. Abciximab as adjunctive therapy to reperfusion in AMI meta-analysis JAMA 2005;293:1759–65

  Recent pooled analysis of 6 studies (602 cases), the early group   higher proportion of pre-PCI TIMI flow grade 3 (20% vs. 12%)   significantly improved ST-segment resolution within 3 h after PCI   moderate but nonsignificant reduction in the risk of death, new MI, or urgent target vessel revascularization at 30 days Godicke J, Flather M Early versus periprocedural administration of abciximab Am Heart J 2005;150:1015   PAMI (Primary Angioplasty in Myocardial Infarction) studies : LV function and survival improvement when TIMI flow grade 3 is present before intervention   improved myocardial salvage   technically easier aspects of the intervention (shorter procedural time & higher proportion of direct stenting)

  ASSENT-4 PCI (Assessment of the Safety and Efficacy Of a New Treatment Strategy for Acute Myocardial Infarction)   PCI with full or reduced dose thrombolytic drugs trial   despite the improvement of initial TIMI flow grade 3, increased rates of death, nonfatal reinfarction, urgent target vessel revascularization, bleeding, and stroke   However, a worse clinical outcome and an increased rate of stroke : not reported in receiving facilitated regimes with platelet glycoprotein IIb/IIIa inhibitors alone

  Intrinsic anticoagulant and fibrinolytic potential of abciximab : antiglycoprotein IIb/IIIa agents possess the ability to dissolve platelet thrombi formed on the collagene surface → enhance infarct-artery patency before mechanical revascularization Goto S, Tamura N, Ishida H. Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi J Am Coll Cardiol 2004;44:316 –23   The positive effect of abciximab on microvascular flow   the prevention of microvascular obstruction potentially caused by embolization of platelet aggregates and microthrombi   improves myocardial blood flow regulation   preserves a coronary blood flow response to acetylcholine

  Study limitations   Prospective, randomized, single-center trial → population size was not powered to detect differences in mortality or hard clinical end points   Operator physicians were not blinded to the treatment assignment (bias of the investigators)   Use of clopidogrel loading dose as standard therapy after undergoing PCI

In patients with AMI treated with primary PCI, early abciximab administration improves pre-PCI angiographic findings and 1-month LV function, possibly by starting early recanalization of the IRA CONCLUSION