Platelet Glycoprotein IIb/IIIa Inhibition as Adjunctive Therapy during Primary Percutaneous Coronary Intervention for Acute St-s

Approximately 1.1 million myocardial infarctions occur annually in the United States and result in about 500,000 deaths. Acute myocardial infarction (AMI) is the result of plaque rupture and thrombus formation, with subsequent occlusion of a coronary artery, resulting in myocardial ischemia and necrosis. The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines classify patients with AMI as those with ST-segment elevation (STEMI), and those with non-ST-segment elevation (NSTEMI), with treatment strategies tailored accordingly.¹ The current standard of care for patients with STEMI involves urgent reperfusion of the infarct-related artery (IRA) by either fibrinolysis or percutaneous coronary intervention (PCI). Survival depends on timely treatment with either modality. Although more limited in availability, PCI has demonstrated a survival advantage when compared with fibrinolytic therapy alone, and has the potential for fewer complications. A recent meta-analysis of 23 randomized clinical trials compared the treatment effect of primary coronary angioplasty versus intravenous fibrinolytic therapy for the treatment of STEMI in 7,739 patients.² The analysis included 8 clinical trials that compared angioplasty with streptokinase; coronary stents were used in 12 of the studies and platelet glycoprotein GP IIb/IIIa inhibitors in 8. Results of the meta-analysis demonstrated that mortality at 3 Additional clinical studies have demonstrated the beneficial effects of GP IIb/IIIa inhibition (primarily abciximab) on myocardial perfusion and recovery of left ventricular function in conjunction with catheter-based mechanical intervention for STEMI.^4–9 The underlying mechanisms for these beneficial effects may be diminished distal embolization of platelet aggregates or inhibition of direct interaction of platelets with the reperfused endothelium by abciximab, particularly when combined with fibrinolysis, which has been shown to increase platelet activation and aggregation.^10–12 To reduce the risk of bleeding complications, weight-adjusted dosing regimens of heparin have been incorporated into the more recent PCI trials, and half-dose fibrinolytic therapy has been proposed when used in combination with GP IIb/IIIa inhibitors. In this issue of the Journal, Lavi et al. present the results of a retrospective analysis of an ongoing registry, addressing the role of GP IIb/IIIa inhibition during primary PCI for STEMI patients.¹³ Over a 7-year period, a total of 402 patients, presenting within 12 hours of symptom onset and who were not treated with pharmacological reperfusion, underwent primary PCI for STEMI. Platelet GP IIb/IIIa inhibition was administered at the operator’s discretion to 287 patients (abciximab 87, eptifibatide 190, tirofiban 10), while 115 underwent primary PCI without IIb/IIIa blockade. Angiographic success (defined as 5 g/dL), or minor (overt signs of hemorrhage with hemoglobin drop of 14 The majority of evidence to date favoring platelet GP IIb/IIIa inhibition during primary PCI for STEMI is with abciximab therapy.^4–9 In fact, a recent meta-analysis of abciximab as adjunctive therapy to reperfusion in STEMI patients demonstrated a significant reduction in 30-day and long-term mortality in patients undergoing primary angioplasty.¹⁵ This is consistent with the earlier abciximab studies outlined by the authors. In contradistinction, earlier experience with eptifibatide therapy during primary PCI for STEMI actually demonstrated an increased rate of subacute thrombosis (SAT) within 3–5 days of the index procedure, with the authors of this study concluding that the dose and infusion duration of eptifibatide required further evaluation in STEMI patients.16 More recently, the INTAMI pilot trial demonstrated that double-bolus eptifibatide given in the emergency room to STEMI patients (mean of 45 minutes prior to PCI), improved TIMI 3 patency without subsequent increase in bleeding complications.17 Further study is needed with these small molecule agents (eptifibatide and tirofiban) in patients presenting with STEMI undergoing primary PCI before definitive recommendations can be made in this setting. The exact dose of unfractionated heparin (UFH) utilized in this study is not reported. UFH was given to maintain an activated clotting time (ACT) of 250–300 seconds which is typically achieved with weight-based algorithms (60–70 IU/kg bolus; 12–15 IU/kg/hour infusion) when concomitant GP IIb/IIIa inhibitor therapy is used, as outlined in the current guidelines.^1,18 Lower dosing regimens with a maximum 4000 IU bolus with 1,000 IU/hour infusion are recommended when UFH is used as an adjunct to fibrinolytic therapy. Lower doses may also be appropriate in women and older adults, particularly when UFH is combined with GP IIb/IIIa inhibitors during PCI.¹⁸ Dual, oral antiplatelet therapy as described in this study (4 weeks) appears adequate for bare metal stents (BMS), and although not specifically reported, one can assume that the majority of these patients received BMS during the time period of the study (January 1996 to November 2003). Oral antiplatelet therapy is currently more prolonged post-PCI primarily due to the high utilization of drug-eluting stents (DES), including unrestricted registry settings where DES are deployed even for lesion subsets (including STEMI) outside of established randomized clinical trial data.^19,20 Considering the limitations as outlined above, the current study adds to our expanding database of information regarding the concomitant use of platelet GP IIb/IIIa inhibitor therapy during primary PCI for STEMI. Ongoing clinical trials of pharmacological “facilitation” of primary PCI for STEMI patients are eagerly awaited with the hope of enhanced myocardial salvage and improved clinical outcomes at any given time of reperfusion.²¹

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