Response to Letter Regarding Article, “Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration: The Comparison of Intracoronary Versus Intravenous Abciximab Administration During Emergency Reperfusion of ST-Segment Elevation Myocardial Infarction (CICERO) Trial”

Abstract

We thank Niccoli et al for their letter, which interestingly suggested that intracoronary administration of abciximab may exert its action in patients with ST-segment elevation myocardial infarction through facilitation of reversible no reflow. Our study was designed to detect a difference in electrocardiographic and angiographic measures of immediate myocardial reperfusion after primary percutaneous coronary intervention, markers that are frequently used in medium-sized randomized studies and show strong correlation with clinical outcome. 1,2 In this regard, we did not include recovery of myocardial perfusion at a later time point as a prespecified end point. It is not our center's routine clinical practice to reevaluate the initial angiographic result and recovery of myocardial perfusion in the infarct-related artery before discharge, either by repeat angiography or by cardiac magnetic resonance imaging. Because the infarct-related artery may have been filmed in additional revascularization procedures only in highly selected cases, we believe that analysis of this small, nonprespecified subset of patients would not produce meaningful results. In fact, an early study has indicated that intracoronary administration of abciximab significantly reduced the primary end point of microvascular obstruction on cardiac magnetic resonance 2 days after primary percutaneous coronary intervention compared with intravenous administration. 3 Therefore, we agree with Niccoli et al that facilitation of reversible no reflow is one of the plausible mechanisms of action of intracoronary abciximab, a hypothesis that may be further tested in ongoing randomized studies on intracoronary versus intravenous abciximab administration that include cardiac magnetic resonance end points. 4 Rationale and design of the INFUSE-AMI study: a 2ϫ2 factorial, randomized, multicenter, single-blind evaluation of intracoronary abciximab infusion and aspiration thrombectomy in patients undergoing percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction.

Intracoronary bivalirudin

“…mechanical thrombectomy combined with various intracoronary drugs) [5] and/or manual thrombectomy combined with distal filters [6] have been previously reported. Gp IIb/IIIa inhibitors and thrombolytics may not be very effective in such situations [7], probably having difficult access to glycoproteins 'masked' in the tightly packed thrombus. A hostile thrombus is frequently the harbinger of no-reflow, a severe compromise of epicardial blood flow despite successful relief of the infarct-related artery obstruction [8].…”

Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI

“…Concerns, however, have been raised that they may also have deleterious effects by interfering with the reperfusion injury signaling pathways, leading to loss of endogenous cardioprotection especially after long-term Table 1 Pharmacologic agents used to reduce infarct size and proposed mechanism of action References Agent Proposed mechanism of action [13][14][15][16] Abciximab Inhibits platelet aggregation and leukocyte adhesion; improves microcirculation [17] Statins Conditioning promoting (by opening of mitochondrial ATP-sensitive channels) and anti-inflammatory effects [18] RAS inhibitors Reduce angiotensin II levels; reduce Ca 2 + overload [19] Anisodamine/ diltiazem Diltiazem: causes endothelium-mediated vasodilatation; reduces metabolic demand by negative inotropic and chronotropic effects; anisodamine: anticholinergic and α 1 -adrenergic receptor antagonist [20] Metoprolol Reduces myocardial oxygen consumption [21] Recombinant human SOD Free radical scavenger [22] Desferoxamine Iron chelator [23] Edaravone Free radical scavenger [24] Allopurinol Inhibitor of xanthine oxidase [25] Hu23F2G (LeukArrest)…”

Newer Pharmaceutical Agents for STEMI Interventions

“…34 The CICERO trial reported that there was a significant improvement in infarct size and myocardial reperfusion as assessed by myocardial blush among patients treated with IC abciximab compared with IV abciximab, though no difference was noted between the two groups in relation to myocardial reperfusion as assessed by resolution of ST segment. 38 Most recently, the Intracoronary Abciximab Infusion and Aspiration Thrombectomy in Patients Undergoing Percutaneous Coronary Intervention for Anterior ST Segment Elevation Myocardial Infarction (INFUSE-AMI) study demonstrated IC administration of abciximab delivered to the infarct lesion site resulted in a significant but mild reduction in infarct size in patients presenting with a large anterior STEMI. 39 There was not, however, any improvement in myocardial reperfusion, ST segment resolution, or 30-day clinical event rates, leaving the clinical utility of this therapy unclear.…”