Platelet glycoprotein IIb/IIIa inhibitor use during percutaneous coronary intervention: IIb or Not IIb,what is the question?

Over the past decade, numerous placebo-controlled randomized clinical trials have documented robust clinical benefits of intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI). This evidence has led to U.S. Food and Drug Administration approval and indication for use of two GP IIb/IIIa inhibitors at the time of PCI, namely, the chimeric monoclonal antibody fragment abciximab (ReoPro, Centocor, Inc. and Eli Lilly & Company) and the cyclic heptapeptide small molecule eptifibatide (Integrilin, COR Therapeutics and Key Pharmaceuticals). Currently, another small molecule GP IIb/IIIa inhibitor, tirofiban (Aggrastat, Merck & Company), which (similar to eptifibatide) is approved for the medical therapy of patients with non-ST segment elevation acute coronary syndromes (ACS), has not received indication for use in the PCI setting. Although the clinical benefits of both abciximab and eptifibatide administered at the time of PCI have been proven in randomized clinical trials, only abciximab has demonstrated a late survival advantage in patients following PCI. Evidence in support of the presence, magnitude and possible mechanisms for abciximab survival advantage is herein reviewed.     

Differential Effects of Citrate Versus PPACK Anticoagulation on Measured Platelet Inhibition by Abciximab, Eptifibatide and Tirofiban

Background: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. Methods/Results: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition.Conclusion: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.     

Time course, magnitude, and consistency of platelet inhibition by abciximab, tirofiban, or eptifibatide in patients with unstable angina pectoris undergoing percutaneous coronary intervention.

Adjunctive platelet glycoprotein IIb/IIIa blockade during percutaneous coronary intervention (PCI) reduces platelet-mediated adverse ischemic outcomes. Although abciximab, eptifibatide, and tirofiban have received U.S. Food and Drug Administration approval for use, these agents differ in their pharmacodynamic profiles. Each of these agents has been compared in randomized trials with placebo for patients undergoing PCI, but no randomized comparative studies of these agents have been performed. We compared ex vivo platelet function by both standard light transmission aggregometry and rapid platelet function assay during and after administration of abciximab, eptifibatide, or tirofiban in approved dose regimens on a randomized basis at the time of PCI in patients with unstable angina pectoris. A reduced intensity of platelet inhibition by light transmission aggregometry was observed for tirofiban compared with either eptifibatide or abciximab. In addition, the 30-minute bolus strategy used for tirofiban was associated with delayed onset of maximal platelet inhibition relative to the initiation of bolus infusion. Whether the trends in platelet function observed in this study will be translated into differences in clinical outcomes awaits definition by larger scale randomized clinical trials comparing these platelet glycoprotein IIb/IIIa inhibitors.     

A Review of Clinical Trials with Eptifibatide in Cardiology

Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. Additional antithrombin therapy should be given in connection with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical trials (IMPACT‐II and ESPRIT) concomitant administration of eptifibatide to patients undergoing percutaneous coronary intervention (PCI) reduced thrombotic complications. In the PURSUIT trial, in patients with non‐ST‐elevation acute coronary syndromes, eptifibatide, compared to placebo, significantly reduced the primary endpoint of death and nonfatal myocardial infarction at 30 days. In patients with STEMI eptifibatide has been studied as an adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue reperfusion. Current studies are evaluating eptifibatide as upstream therapy in high‐risk patients with NSTE‐ACS, in the EARLY‐ACS and in comparison with abciximab in patients with primary PCI in the EVA‐AMI trial.     

Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting

OBJECTIVES: We sought to investigate whether abciximab, tirofiban and eptifibatide achieve comparable antiplatelet effects with coronary stenting. BACKGROUND: The glycoprotein (GP) IIb/IIIa antagonists abciximab, tirofiban and eptifibatide differ in chemical structure, binding site and pharmacokinetics. METHODS: Sixty patients undergoing coronary stenting were randomly assigned to abciximab (bolus 0.25 mg/kg body weight, infusion 10 microg per min for 12 h), tirofiban (bolus 10 microg/kg, infusion 0.15 microg/kg per min for 72 h) or eptifibatide (bolus 180 microg/kg, infusion 2 microg/kg per min for 72 h). We took serial blood samples to analyze platelet function by using flow cytometry, turbidimetric aggregometry and the rapid platelet-function assay (RPFA). RESULTS: As assessed by RPFA, platelet aggregation after 2 h of infusion was reduced to 5.9 +/- 7.8% (mean +/- SD) of baseline by abciximab, to 5.0 +/- 5.4% by tirofiban and to 7.8 +/- 7.1% by eptifibatide (p = 0.42). Turbidimetric aggregometry with adenosine diphosphate stimulation yielded similar results, whereas percent inhibition of platelet aggregation after thrombin receptor stimulation was 45.8 +/- 16.8% with abciximab, 51.3 +/- 17.6% with tirofiban and 52.9 +/- 14.8% with eptifibatide (p = 0.37). Tirofiban and eptifibatide maintained their level of platelet inhibition during infusion. Flow cytometry revealed that the reduction in the monocyte-platelet interaction by abciximab, tirofiban and eptifibatide was not significantly different (20.0 +/- 21.9%, 23.8 +/- 18.2% and 21.0 +/- 19.8%, respectively; p = 0.87). CONCLUSIONS: Abciximab, tirofiban and eptifibatide, at currently recommended doses, achieved similar levels of inhibition of platelet aggregation and a similar reduction in the platelet-monocyte interaction.     

Current knowledge of the platelet glycoprotein IIb/IIIa receptor antagonists for the treatment of coronary artery disease

Understanding of the pivotal role of the platelet surface membrane glycoprotein (GP) IIb/IIIa receptor in platelet aggregation at the injured coronary plaque in acute coronary syndromes has led to recent pharmacologic strategies that focus on inhibition of this final common pathway. Several intravenous medications directed specifically at this receptor (called platelet GP IIb/IIIa receptor antagonists; GPAs) have emerged. These include the human-murine chimeric monoclonal antibody Fab fragment abciximab, the peptide antagonist eptifibatide and the peptidomimetics tirofiban and lamifiban. To date, over 33,000 patients have been studied with these compounds in 11 large, randomized placebo controlled trials which have established the effectiveness of these drugs in conditions where platelet aggregation and thrombosis play major contributing roles such as in high-risk coronary intervention, myocardial infarction and unstable angina. GPAs have been proven to be effective in reducing ischemic complications when used as an adjunct to percutaneous coronary revascularization or the management of acute ischemic syndromes. They are well tolerated and safe, provided concomitant use with other antithrombotics (e.g. heparin) is carefully managed and platelet counts are monitored.     

Update on Glycoprotein IIb/IIIa Blockade in Endovascular Interventions

Platelet aggregation plays a central role in the ischemic complications of percutaneous coronary interventions (PCI) and the acute coronary syndromes (ACS). Although aspirin and heparin have been effective at decreasing adverse events in these settings, the perceived need for more potent inhibition of platelet aggregation has led to targeting of the platelet surface membrane glycoprotein IIb/IIIa (GP IIb/IIIa) receptor. Several agents have been developed; four: abciximab, tirofiban, eptifibatide, and lamifiban have been tested in clinical trials. Overall, the positive findings of these studies have supported the hypothesis that enhanced platelet blockade leads to improved clinical outcomes in the settings of PCI and ACS. In this article, an overview of the various GP IIb/IIIa receptor inhibitors is presented. The clinical trials of these agents as adjunctive therapy for patients undergoing PCI and in treatment of acute myocardial infarction are reviewed. Practical considerations relating to clinical efficacy, drug safety, and economic issues are discussed.     

Variability in extent of platelet function inhibition after administration of optimal dose of glycoprotein IIb/IIIa receptor blockers in patients undergoing a high-risk percutaneous coronary intervention

The Ultegra Rapid Platelet Function Assay was used to measure the inhibition of platelet aggregation at baseline and 10 minutes and 8 hours after starting therapy in 114 patients undergoing high-risk percutaneous coronary intervention with the planned use of a glycoprotein IIb/IIIa inhibitor. The abciximab-treated patients received a 0.25 mg/kg bolus, followed by a 0.125 microg/kg/min infusion for 12 hours; the eptifibatide-treated patients received 2 boluses of 180 microg/kg administered 10 minutes apart, followed by a 2 microg/kg/min infusion for 24 hours; the tirofiban-treated patients received a 25 microg/kg bolus, followed by a 0.15 microg/kg/min infusion for 18 hours. Ten minutes after starting therapy, the mean level of platelet inhibition was 86 +/- 9% for abciximab, 92 +/- 6% for eptifibatide, and 95 +/- 5% for tirofiban (p <0.001); > or =95% platelet inhibition was achieved in 29% of the patients treated with abciximab, 44% of those receiving eptifibatide, and 68% of the those receiving tirofiban (p = 0.02). In conclusion, at the evaluated doses, tirofiban seemed to be the most effective drug in achieving "optimal" platelet inhibition very early after percutaneous coronary intervention.     

Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease

New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents. During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.     

Profound thrombocytopenia associated with tirofiban: case report and review of literature

Platelet glycoprotein (GP)IIb/IIIa inhibitors prevent fibrinogen binding and platelet aggregation. Inhibition of platelet activity at the injured coronary plaque is a target for novel therapeutic strategies. They decrease ischemic complications associated with non-ST-segment elevation acute coronary syndromes and percutaneous coronary intervention. Thrombocytopenia is a serious complication well described with the use of the prototype GP IIb/IIIa inhibitor abciximab. Its association with other agents of this class has been underemphasized. It is important to monitor platelet counts closely after initiation of GP IIb/IIIa inhibitor therapy, not only for abciximab, but also for small molecule inhibitors such as eptifibatide and tirofiban. Monitoring of platelet counts at 2 to 6 hours and 24 hours will detect most cases of acute thrombocytopenia. Adverse events may be prevented by prompt discontinuation of GP IIb/IIIa inhibitor therapy. The authors present a case of profound thrombocytopenia after the administration of tirofiban in the treatment of a patient with an acute coronary syndrome.     

Platelet receptor glycoprotein IIb/IIIa inhibition with eptifibatide in a patient with thrombocytopenia after treatment with abciximab

Clinical experience suggests that patients treated with the glycoprotein (GP) IIb/IIIa inhibitor abciximab (ReoPro , Eli Lilly and Company, Indianapolis, Indiana) may be at increased risk of thrombocytopenia. This case report details the successful use of the GP IIb/IIIa inhibitor eptifibatide (Integrilin , COR Therapeutics, South San Francisco, California) in a patient who developed acute thrombocytopenia (platelet count: 67,000/mm3) approximately 10 hours after initiation of abciximab therapy. Five hours after abciximab was discontinued, platelet count returned to normal (191,000/mm3) and eptifibatide was started because of persistent electrocardiographic evidence of ischemia. The patient underwent diagnostic catheterization during eptifibatide therapy, which was administered for approximately three days. Four days after the initial course of therapy with eptifibatide was discontinued, percutaneous revascularization with adjunct eptifibatide was performed. During both courses of eptifibatide therapy, platelet counts remained in the normal range (> 100,000/mm3) and no adverse ischemic or bleeding events occurred.     

Pharmacodynamics,safety, and clinical effects of a novel glycoprotein IIb/IIIa antagonist framon during high risk coronary angioplasty

Preparation framon [F(ab')2 fragments of the anti-glycoprotein (GP) IIb/IIIa monoclonal antibody (FRaMon)] blocks fibrinogen binding to GP IIb/IIIa and platelet aggregation. Dynamics of platelet aggregation inhibition, safety, and clinical effects of framon were studied in high-risk coronary angioplasty. Twenty seven patients underwent angioplasty with framon, 29 - with abciximab and 28 - with no GP IIb/IIIa antagonists. Framon at 0.2 mg/kg (n=16) and 0.25 mg/kg (n=11) bolus administration inhibited platelet aggregation induced by 20 mcM ADP by more than 90%, 80%, 60% and 30% in comparison with the predrug level 1, 12, 24 and 72 h after injection, respectively. Almost the same dynamics of aggregation inhibition was observed upon abciximab administration at 0.25 mg/kg bolus + 0.125 mcg/kg/min infusion for 12 h. No signs of individual intolerance and side effects including allergic reactions and bleedings were detected in patients treated with framon. Slight decrease of platelet count (15-20%) was observed on the first day after framon administration. Antibodies against framon were detected in 1 out of 22 tested patients. Free (nonbound to platelets) framon was completely removed from the circulation 12 h after injection. The number of endpoints (death, myocardial infarction and indications for repeat revascularization) within 1 year after angioplasty was approximately the same in the groups with framon and abciximab - 7 of 25 (28%) and 7 of 28 (25%), respectively, and more than 1.5 fold higher in the group without GP IIb/IIIa blockers - 12 of 27 (44,4%).     

Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study).

This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.     

GP IIb/IIIa inhibitors during primary percutaneous coronary intervention for STEMI: New trial and registry data

Primary percutaneous coronary intervention (PCI) with adjunctive glycoprotein (GP) IIb/IIIa receptor inhibitor therapy administered in the cardiac catheterization laboratory is the optimal reperfusion strategy for patients with ST-elevation myocardial infarction. Most available data regarding these agents are from trials comparing abciximab to placebo alone. Noninferiority trials comparing small-molecule GP IIb/IIIa receptor inhibitors, such as tirofiban and eptifibatide with abciximab, have used markers for myocardial reperfusion as primary end points but are underpowered to detect significant differences in hard clinical outcomes. Such a trial would need to enroll a very large number of patients and thus make it practically impossible to perform. Registry data reveal that most patients undergoing primary PCI are treated with small-molecule GP IIb/IIIa receptor inhibitors in clinical practice, and no observed difference is observed in safety and efficacy when compared with patients treated with abciximab therapy.     

Therapeutic heparin concentrations augment platelet reactivity: implications for the pharmacologic assessment of the glycoprotein IIb/IIIa antagonist abciximab

BACKGROUND: This study evaluated the effect of heparin on the platelet reactivity and the pharmacodynamic profile of abciximab. METHODS AND RESULTS: Ex vivo studies were performed on patients undergoing elective percutaneous coronary intervention (n = 26) who were at moderate to high risk of ischemic complications. Patients received a 12,000-U bolus of heparin followed by a 0.25-mg/kg bolus of abciximab. Before abciximab treatment, platelet aggregation responses to a variety of stimuli were assessed immediately before and 10 minutes after the heparin bolus. Heparin increased platelet aggregation to 2 and 5 micromol/L adenosine diphosphate (ADP) and 5 microg/mL collagen by 36%, 25%, and 46%, respectively (P < or =.001), but did not influence platelet reactivity to thrombin receptor-activating peptide or 20 micromol/L ADP and had no appreciable effect on platelet surface glycoprotein (GP) IIb/IIIa receptor numbers. To assess the impact of heparin on the pharmacodynamic profile of abciximab, GP IIb/IIIa receptor blockade and platelet aggregation inhibition estimates obtained after abciximab administration were calculated relative to the basal levels observed both before and after the heparin bolus. At 2 and 24 hours after the abciximab bolus, GP IIb/IIIa receptor blockade measurements normalized to either the preheparin or postheparin baseline determinations were equivalent. For all ADP concentrations tested, the 2-hour post-abciximab bolus platelet aggregation inhibition estimates based on the preheparin and postheparin baseline values were comparable. However, for 2 and 5 micromol/L ADP, the 24-hour post-abciximab platelet aggregation inhibition measurements based on preheparin baseline values were significantly lower than postheparin baseline determinations (both P < or =.003). In vitro studies revealed that therapeutic heparin doses induced a concentration-dependent reduction in the extent of platelet inhibition produced by amounts of abciximab that elicit partial inhibition of platelet aggregation. However, at abciximab concentrations that achieved platelet aggregation blockade of >80%, the levels of inhibition of platelet aggregation in the presence and absence of heparin were equivalent. CONCLUSIONS: The cumulative ex vivo and in vitro data indicate that for certain stimuli, heparin alters the platelet inhibitory profile of abciximab at concentrations of the agent that yield partial suppression of platelet function.     

Safety of glycoprotein IIb/IIIa inhibitors in urgent or emergency coronary artery bypass graft surgery

Approximately 2% to 4% of patients undergo urgent or emergency coronary artery bypass grafting (CABG) for complications of percutaneous coronary intervention (PCI) after treatment with glycoprotein (GP) IIb/IIIa inhibitors. The pharmacokinetic and pharmacodynamic properties of GP IIb/IIIa inhibitors play a large role in determining the safety of their use in the setting of urgent or emergency CABG procedures. Emergency or urgent CABG after treatment with the GP IIb/IIIa inhibitor, abciximab, may be associated with increased risk of hemorrhage and the requirement of platelet transfusions if surgery is performed within 12 h of abciximab discontinuation. Eptifibatide is associated with a similar risk compared with placebo, even when surgery is performed within 2 h of eptifibatide cessation. Limited data for tirofiban show that bleeding is not increased when compared with acetylsalicylic acid or heparin. Eptifibatide and tirofiban appear to have favourable safety profiles compared with abciximab in the setting of emergency or urgent CABG after failed PCI.     

Incidence and time course of thrombocytopenia with abciximab and eptifibatide in patients undergoing percutaneous coronary intervention

Thrombocytopenia is recognized as a potential adverse effect in patients treated with glycoprotein IIb/IIIa inhibitors. We monitored platelet counts at baseline and at 10 minutes and at 1, 8, and 24 hours after initiation of therapy with either abciximab (n = 74) or eptifibatide (n = 26) in a series of 100 consecutive patients who underwent percutaneous coronary intervention. Thrombocytopenia (platelet count <100,000 m(3) occurred in 11 patients treated with abciximab (15%) and in none of those treated with eptifibatide. The inhibition of platelet adhesion to fibrinogen-coated material by abciximab and eptifibatide was similar, indicating that the reduction in platelet count with abciximab is unrelated to inhibition of platelet function.     

Update on the treatment with platelet antiaggregation agents]

Antiplatelet agents are primarily used to prevent and treat arterial thrombosis. Their mechanism of action is related to the interaction with metabolism of arachidonic acid, the increase of intraplatelet cAMP or the antagonism of ADP or GP IIb/IIIa receptors. Aspirin was one of the first agents to be adopted and it remains as the standard therapy with the higher amount of available clinical information. Following aspirin, ADP receptor antagonists like ticlopidine and more recently clopidogrel have been introduced. In the CAPRIE study, clopidogrel was shown to be more effective than aspirin in the prevention of vascular events in patients with atherothrombotic disease. The newer antiplatelet agents are GP IIb/IIIa receptor antagonists like eptifibatide, tirofiban and abciximab, which act at the end of the common pathway of platelet aggregation. Their benefits after intravenous administration have been shown in the treatment of acute coronary syndrome and percutaneous coronary angioplasty. The potential application of GIIb/IIIa targeted therapy might theortically be expanded by the new class of oral GP IIb/IIIa antagonists. However, their performance in clinical trials has been disappointing.     

An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death.

We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting.

A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%).

Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes.

The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.     

Platelet glycoprotein IIb/IIIa inhibitors in coronary artery disease

BACKGROUND: Inhibition of platelet activity at the injured coronary plaque is a target for novel therapeutic strategies. One of these mechanisms is the blockade of the platelet surface membrane glycoprotein (GP) IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban. RESULTS: During percutaneous coronary intervention, an absolute reduction of 1.5-6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested. Treatment effect is achieved early with every modality of revascularization and maintained over the long-term up to 3 years. Increased bleeding risk may be minimized by reduction and weight adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5-3.2% reductions in 30-day rates of death or myocardial infarction have been achieved with 2- to 4-day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. CONCLUSION: Thus, blockade of the platelet GP IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.