Platelet glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction

There are many limitations to reperfusion therapy for acute myocardial infarction. Preliminary studies have explored the potential of using more potent antiplatelet therapy. Abciximab, eptifibatide, and lamifiban are new agents that inhibit platelet glycoprotein IIb/IIIa, which serves as the final common pathway for platelet aggregation. Infarct artery patency occurs more rapidly, normal coronary blood flow is more often restored, and reperfusion is more stable when these agents are used with standard- or reduced-dose fibrinolytic therapy. Moreover, abciximab monotherapy has thrombolytic activity and facilitates primary angioplasty or stenting. Further studies are needed to define safety, efficacy, and cost effectiveness.     

Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention in acute myocardial infarction

Although percutaneous coronary intervention (PCI) following full-dose thrombolytic therapy (rescue angioplasty) is a common procedure, there is ample controversy regarding the usefulness of the procedure. Moreover, few data are available concerning the safety and efficacy of concomitant treatment with glycoprotein (GP) IIb/IIIa inhibitors in these patients. The aim of the present study was to compare the clinical outcomes of patients who underwent rescue PCI with stents and were treated with GP IIb/IIIa inhibitors. A total of 59 consecutive patients underwent rescue PCI at our institution during the study period, 29 patients (49.2%) were treated concomitantly with a GP IIb/IIIa inhibitor and 30 patients (50.8%) were not. Baseline clinical characteristics were similar between the two groups. In-hospital outcomes regarding death, reinfarction and the need for urgent target vessel revascularization was significantly lower in patients treated with GP IIb/IIIa inhibitors compared to those who were not treated (3.4% vs. 26.7%; p = 0.01, respectively). However, GP IIb/IIIa inhibitor administration was not an independent predictor of better outcomes by multivariate analysis. There was a higher rate of major bleeding complications in patients who received GP IIb/IIIa inhibitors, though it did not achieve statistical significance (6.9% vs. 0%; p = 0.14, respectively). The composite endpoint of major, minor bleeding and vascular complications was similar in both groups (24.1% vs. 16.7%; p = 0.48). In conclusion, the administration of GP IIb/IIIa inhibitors in patients undergoing rescue PCI after failed thrombolysis with stents was safe and may have a beneficial effect on 30-day event-free survival rates, without a significant increase in bleeding or vascular complications. These results warrant further investigation.     

Long-term recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

AIMS: To investigate changes in left ventricular function in the first 6 months after acute myocardial infarction treated with primary angioplasty. To assess clinical variables, associated with recovery of left ventricular function after acute myocardial infarction. METHODS: Changes in left ventricular function were studied in 600 consecutive patients with acute myocardial infarction, all treated with primary angioplasty. Left ventricular ejection fraction was measured by radionuclide ventriculography in survivors at day 4 and after 6 months. Patients with a recurrent myocardial infarction within the 6 months were excluded. RESULTS: Successful reperfusion (TIMI 3 flow) by primary angioplasty was achieved in 89% of patients. The mean ejection fraction at discharge was 43.7%+/-11.4, whereas the mean ejection fraction after 6 months was 46.3%+/-11.5 (P<0.01). During the 6 months, the mean relative improvement in left ventricular ejection fraction was 6%. An improvement in left ventricular function was observed in 48% of the patients; 25% of the patients had a decrease, whereas in the remaining patients there was no change. After univariate and multivariate analysis, an anterior infarction location, an ejection fraction at discharge < or =40% and single-vessel disease were significant predictors of left ventricular improvement during the 6 months. CONCLUSIONS: After acute myocardial infarction treated with primary angioplasty there was a significant recovery of left ventricular function during the first 6 months after the infarction. An anterior myocardial infarction, single-vessel coronary artery disease, and an initially depressed left ventricular function were independently associated with recovery of left ventricular function. Multivessel disease was associated with absence of functional recovery. Additional studies, investigating complete revascularization are needed, as this approach may potentially improve long-term left ventricular function.     

Association of glycoprotein IIb/IIIa inhibitors and long-term survival following administration during percutaneous coronary intervention for acute myocardial infarction

Objectives: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. Background: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. Methods: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. Results: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034–0.729; P = 0.018). Conclusions: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality.     

Controversies surrounding platelet glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention and acute coronary syndromes

Platelet-dependent thrombosis is an important part of the pathophysiology of both percutaneous coronary interventions (PCI) and acute coronary syndrome (ACS). Data support the use of acute therapies that interfere with platelets to provide clinical benefit to patients presenting with acute cardiovascular disease. The discovery of platelet glycoprotein (GP) IIb/IIIa receptor antagonists has been a major advance in the pharmacotherapy for patients undergoing PCI and those presenting with ACS without ST-segment elevation. This article will cover the role of platelets in acute cardiovascular disease, as well as the discovery and development of the platelet GPIIb/IIIa inhibitors. The major focus of this article will be on examining key lessons from the trials in each of these areas as well as presenting a series of questions that still require answers from either ongoing or future research.     

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes

Antagonists of the platelet fibrinogen receptor glycoprotein IIb/IIIa are potent inhibitors of platelet function and provide marked protection from ischemic events in patients undergoing PCI. These agents are also of benefit in patients with unstable angina or non-ST segment elevation myocardial infarction (MI) and provide a 9% reduction in the combined endpoint of 30-day death or MI. This benefit is most marked in patients undergoing early PCI or those at increased risk due to history of diabetes or elevation of the cardiac marker troponin. Based on these findings, the combined American Heart Association and American College of Cardiology guidelines on the management of unstable angina and non-ST segment elevation MI recommend intravenous GPIIb/IIIa in patients in whom PCI is planned particularly those with elevated troponin or diabetes. The use of these agents is associated with a slight increase in major bleeding and in rare instances thrombocytopenia that usually resolves quickly after therapy is discontinued.     

替罗非班对急性冠脉综合征患者血小板活化度的影响

目的:评价GPⅡb/Ⅲa受体拮抗剂(盐酸替罗非班)对急性冠脉综合征(ACS)患者血小板活化度的影响及临床安全性。方法:受试组患者为来自2005年1月～2008年1月我院就诊的急性非ST段抬高型心肌梗塞和不稳定型心绞痛ACS患者,共126例,接受盐酸替罗非班持续泵入24～48h,根据年龄、性别选取同期就诊的稳定型心绞痛冠心病患者112例作为对照组。应用流式细胞仪分别对受试组和对照组患者CD61、CD62p、活化的GPⅡb/Ⅲa(PAC-1)的表达情况进行分析。结果:受试组CD61、PAC-1指标应用替罗非班1.5～2h,10h,48h比用药前明显降低(P均0.01),而对照组在治疗前后无明显变化;CD61仅用药1.5h时两组间比较有显著差异(P0.001);受试组PAC-1水平在治疗1.5～2h,10h时明显下降(P0.05),在48h又出现明显升高(P0.05)。结论:急性冠脉综合征患者应用GPⅡb/Ⅲa受体拮抗剂可改善长期的临床预后,同时我们的研究也显示替罗非班治疗急性冠脉综合症是有效的和安全的。     

Role of oral blockade of platelet glycoprotein IIb/IIIa on neutrophil activation in patients with acute coronary syndromes

Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5–7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation—as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5–7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.     

Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes

Acute coronary syndromes are a leading cause of hospitalization in industrialized countries. Current antithrombotic therapy focuses on relatively weak antiplatelet agents and heparin. The advent of inhibitors of the platelet glycoprotein IIb/IIIa receptor, the final common pathway for aggregation, provides a new therapeutic modality. Clinical trials with a total of more than 18,000 patients have clearly shown the benefits of intravenous IIb/IIIa blockade. Overall, at 30 days, 13 fewer deaths or myocardial infarctions occurred for every 1000 patients treated in these trials. This favorable outcome was extended to 6 months, resulting in 16 fewer such events per 1000 patients treated. Importantly, these benefits were not accompanied by an excessive occurrence in bleeding complications or thrombocytopenia. To further improve outcomes in this high-risk group of patients, strategies pertaining to prolonged periods of vessel passivation with oral formulations and early or delayed invasive approaches are being studied.     

Emergency coronary artery bypass grafting in patients with acute myocardial infarction treated with glycoprotein IIb/IIIa receptor inhibitors

Glycoprotein (GP) IIb/IIIa receptor inhibitors before primary angioplasty in patients with ST-elevation acute myocardial infarction (STEMI) are recommended by current guidelines. Thus, an increasing number of patients receive these drugs before coronary angiography, particularly if a between-hospital transfer is needed. However, when coronary anatomy is unsuitable for angioplasty, emergency coronary artery bypass grafting (CABG) under GP IIb/IIIa inhibitor treatment may be needed, with a potential increase in bleeding risk. Abciximab has a long duration of action, because of its high-affinity binding to GP IIb/IIIa receptors. Initial retrospective studies reported a higher incidence of major bleeding during emergency CABG after abciximab administration, leading to the recommendation of delaying surgery >12 h. However, data from the prospective trials on abciximab do not confirm the increase in bleeding risk, and current evidence shows that emergency surgery can be performed safely soon after abciximab cessation. Monitoring of activated clotting time during surgery and platelet transfusion in case of postoperative relevant bleeding are the only measures needed. No data are available on emergency surgery in patients with STEMI treated with eptifibatide or tirofiban. However, their short-lasting effects and the results of trials on non-ST-elevation acute coronary syndromes suggest that they could even reduce postoperative bleeding by preventing platelet consumption during cardiopulmonary bypass. In conclusion, the early administration of GP IIb/IIIa inhibitors, in particular of abciximab, in patients with STEMI in whom primary angioplasty is planned should not be discouraged because of the potential bleeding risk in case of emergency CABG.