Adjunctive Antiplatelet Therapy during Rescue PCI

The treatment of ST-segment elevation myocardial infarction (STEMI) continues to evolve due to the adoption of antiplatelet and anticoagulation regimens in combination with pharmacologic (fibrinolysis) and/or mechanical reperfusion. Rapid, complete and sustained restoration of infarct-related artery (IRA) blood flow and myocardial perfusion directly impacts patient outcomes, with improvement in left ventricular function and reduction in infarct size and mortality.^1–5 Current fibrinolytic regimens appear to have reached a therapeutic ceiling, with normal (TIMI grade 3) IRA flow being restored at 90 minutes in only 50–60% of patients and normal myocardial perfusion (myocardial blush grade 3) in only 30–45%.^4,5 While primary percutaneous coronary intervention (PCI) may lead to the restoration of normal IRA flow in 85–95% of patients, myocardial perfusion often remains abnormal.^6,7 Recent randomized controlled trial data support the integration of angiography and PCI into a sequential reperfusion-revascularization strategy following fibrinolysis on either a “rescue”⁸ or immediate/early^9,10 basis. As many centers lack PCI facilities, the strategy of adding glycoprotein (GP) IIb/IIIa inhibitors to facilitate the sequence of pharmacological and mechanical reperfusion would appear attractive. There is now considerable evidence supporting the use of GP IIb/IIIa inhibitors during primary PCI for acute myocardial infarction (AMI).^11,12 These data suggest that GP IIb/IIIa antagonists, specifically abciximab, inhibit platelet aggregation, rethrombosis and reocclusion following successful PCI. These agents also disaggregate platelet-rich thrombi that may be lodged in the epicardial vessel or which may have embolized to the distal vascular bed and thus, impede microvascular perfusion despite the presence of patent epicardial coronary arteries. Data regarding the safety of administering GP IIb/IIIa antagonists to patients with AMI in whom fibrinolytic therapy has already been initiated are more limited.^13–15 Specifically, there are no large-scale prospective trials that answer the question of whether GP IIb/IIIa inhibitor use during rescue PCI (following failed fibrinolysis) provides benefit. In the current issue of the Journal, Gruberg et al. present the results of a small, retrospective study examining the utilization of GP IIb/IIIa inhibitors during rescue PCI.¹⁶ From January 2001 to August 2004, 59 consecutive patients undergoing PCI following full-dose fibrinolytic therapy for STEMI were included. Failure of reperfusion was defined 1 hour after the administration of fibrinolytic therapy if the ST-segment resolution was less than or equal to 50%. Twenty-nine patients (49%) received adjunctive GP IIb/IIIa inhibition during PCI, while 30 (51%) did not. The decision to utilize GP IIb/IIIa inhibition in these 29 patients, as well as selection of the specific agent (abciximab 15, eptifibatide 13, tirofiban 1), was arbitrary and at the discretion of the operator. All patients received aspirin (325 mg) as well as unfractionated heparin (UFH) weight-adjusted bolus (100 U/kg; or 50–60 U/kg if IIb/IIIa was administered). Clopidogrel (300 mg load followed by 75 mg daily) was administered following the procedure and all patients were treated with bare metal stents. Clinical success defined as successful revascularization in the absence of death, reinfarction or emergency coronary artery bypass graft surgery, was obtained in all patients with restoration of normal TIMI 3 flow in 90% of patients in both groups. In-hospital clinical endpoints such as death and the need for urgent target vessel revascularization (TVR) were numerically lower in patients treated with GP IIb/IIIa inhibition; with the composite endpoint (death, reinfarction, urgent TVR) demonstrating a significant reduction (26.7% vs. 3.4%; p = 0.01). Multivariate analysis to 30 days failed to demonstrate any independent predictive benefit to GP IIb/IIIa utilization. Major bleeding complications were numerically higher in the GP IIb/IIIa group (p = 0.14), while the composite endpoint of major, minor bleeding and vascular complications was similar between groups (24.1% vs. 16.7%; p = 0.48). The main limitations of the present study are its retrospective, non-randomized nature and small sample size. No information is provided on risk stratification or the decision process used to determine utilization of GP IIb/IIIa inhibition in these patients. The significant reduction in the composite endpoint of death, reinfarction and urgent TVR, was not surprisingly driven by a reduction in the need (in-hospital) for TVR in the GP IIb/IIIa treatment group. This is consistent with the known risk of IRA re-occlusion following fibrinolytic therapy or PCI and the beneficial role of platelet inhibition in reducing this event. In the CADILLAC trial, early thrombosis following coronary stent deployment was eliminated by the administration of abciximab.¹⁷ Importantly, bleeding complications were not significantly different between the two treatment groups with the administration of GP IIb/IIIa inhibition averaging approximately 3 hours after full-dose fibrinolysis. However, an important caveat is that all the patients in the present study were less than or equal to 70 years of age. Elderly patients (greater than or equal to 75 years) may be at higher bleeding risks when utilizing this GP IIb/IIIa rescue PCI strategy. Recent data suggest an increased bleeding risk when GP IIb/IIIa inhibitors are administered following fibrinolysis.^12–14 Finally, the small sample size, and particularly the small number of clinical events, makes interpretation of the multivariate analysis for outcomes to 30 days problematic. Unfortunately, no definitive conclusions regarding the role of adjunctive GP IIb/IIIa inhibition during rescue PCI can be made from this study. Early PCI after clinically failed fibrinolysis improves IRA patency, may salvage myocardium and improve long-term outcome. Adjunctive platelet GP IIb/IIIa inhibition, especially with abciximab, during primary PCI confers a 50% risk reduction in the incidence of ischemic complications. At present, data in support of benefit for GP IIb/IIIa inhibition during rescue PCI are non-randomized and larger, randomized trial data will be required before recommendations can be made as to the safe and effective utilization of these agents following failed fibrinolytic therapy for STEMI.

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