Platelet glycoprotein IIb/IIIa receptor antagonists

The molecular understanding of platelet function, together with an appreciation of the role of platelet thrombus in the pathogenesis of acute coronary syndromes (ACS) and abrupt vessel closure following coronary intervention, lead to the development of the class of agents now referred to as platelet glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors. Currently three parenteral GP IIb/IIIa inhibitors are licensed for use in patients undergoing coronary intervention or as empirical therapy in non-ST elevation ACS (unstable angina and non-Q wave myocardial infarction). Clinical trials using these agents in patients undergoing coronary interventions have demonstrated a consistent reduction in ischaemic end points at 30 days that is sustained during long-term follow-up. Similar benefits have been found in patients with ACS who are managed medically or who proceed to revacularization. Studies using prolonged platelet inhibition using oral GP IIb/IIIa inhibitors in patients following coronary intervention or with ACS have produced disappointing results. Further investigation with existing and newer oral agents are ongoing. The use of GP IIb/IIIa inhibitors in combination with fibrinolytic agents for optimal reperfusion in patients with acute ST-elevation myocardial infarction (MI) is an active area of interest. Angiographic outcomes with this approach have been encouraging and clinical outcome data are awaited. Beyond efficacy, GP IIb/IIIa inhibitors have proven to be safe for clinical use. Haemorrhagic complications and thrombocytopenia are the most common adverse events, though infrequent. Unresolved issues regarding drug dosing, monitoring of effect, duration of therapy, head-to-head comparisons of agents, and use of adjunctive therapies are the subject of ongoing studies.     

Platelet glycoprotein IIb/IIIa inhibitors during percutaneous coronary interventions: a pharmacological and clinical review

One of the most significant advances of the last decade has been the development of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors. A large series of randomised, controlled clinical trials of these agents have shown a significant reduction in ischaemic events, not only in acute coronary syndrome patients, but also in patients who undergo elective percutaneous coronary interventions. Even though the use of oral antiplatelet and antithrombotic therapies in addition to percutaneous coronary interventions have had a significant impact in clinical outcomes after acute coronary syndromes, the use of GP IIb/IIIa inhibitors provide additional protection against recurrent ischaemia and has been identified as the pivotal mediator of platelet aggregation, making it a logical target for the control of platelet response to vascular injury. A series of key trials performed over the last few years with GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention, have shown a reduction in the risk of short-term death and non-fatal myocardial infarction. The pharmacology and molecular basis of GP IIb/IIIa receptor inhibition and the use of these agents in patients undergoing percutaneous coronary intervention (during acute coronary syndromes and in elective procedures) and their safety issues will be reviewed. A special emphasis has been made on the role of these agents in diabetic patients and their beneficial effect in reducing peri-procedural creatine kinase myocardial band fraction elevation and associated complications.     

Low molecular weight heparins combined with platelet glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndromes

Clinical trials of several platelet glycoprotein (GP) IIb/IIIa receptor inhibitors have demonstrated an unequivocal benefit of this potent antithrombotic therapy in high-risk patients with acute coronary syndromes (ACS) as well as in those undergoing percutaneous coronary intervention. In all of these major trials, however, GP IIb/IIIa inhibitors were used in combination with unfractionated (UF) heparin. Low molecular weight heparins (LMWH) have several advantages over UF heparin therapy, making them attractive alternatives for use in combination with GP IIb/IIIa inhibitors. In the INTegrelin and Enoxaparin Randomized assessment of Acute Coronary syndrome Treatment (INTERACT) study, combination therapy using the GP IIb/IIIa inhibitor eptifibatide (Integrilin^®) and the LMWH enoxaparin (Lovenox^®) in patients with high-risk non-ST-segment elevation ACS, resulted in improved outcomes compared to the currently recommended therapy of UF heparin, with better safety results. It is anticipated that the LMWHs may soon replace the traditional UF heparin for combination therapy with GP IIb/IIIa inhibitors in the medical stabilisation of patients with ACS. Results of other ongoing studies of LMWH combinations with other GP IIb/IIIa inhibitors and in the setting of percutaneous coronary intervention are awaited.     

Platelet glycoprotein IIb/IIIa inhibitors during percutaneous coronary interventions: a pharmacological and clinical review

One of the most significant advances of the last decade has been the development of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors. A large series of randomised, controlled clinical trials of these agents have shown a significant reduction in ischaemic events, not only in acute coronary syndrome patients, but also in patients who undergo elective percutaneous coronary interventions. Even though the use of oral antiplatelet and antithrombotic therapies in addition to percutaneous coronary interventions have had a significant impact in clinical outcomes after acute coronary syndromes, the use of GP IIb/IIIa inhibitors provide additional protection against recurrent ischaemia and has been identified as the pivotal mediator of platelet aggregation, making it a logical target for the control of platelet response to vascular injury. A series of key trials performed over the last few years with GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention, have shown a reduction in the risk of short-term death and non-fatal myocardial infarction. The pharmacology and molecular basis of GP IIb/IIIa receptor inhibition and the use of these agents in patients undergoing percutaneous coronary intervention (during acute coronary syndromes and in elective procedures) and their safety issues will be reviewed. A special emphasis has been made on the role of these agents in diabetic patients and their beneficial effect in reducing peri-procedural creatine kinase myocardial band fraction elevation and associated complications.     

Low molecular weight heparins combined with platelet glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndromes

Clinical trials of several platelet glycoprotein (GP) IIb/IIIa receptor inhibitors have demonstrated an unequivocal benefit of this potent antithrombotic therapy in high-risk patients with acute coronary syndromes (ACS) as well as in those undergoing percutaneous coronary intervention. In all of these major trials, however, GP IIb/IIIa inhibitors were used in combination with unfractionated (UF) heparin. Low molecular weight heparins (LMWH) have several advantages over UF heparin therapy, making them attractive alternatives for use in combination with GP IIb/IIIa inhibitors. In the INTegrelin and Enoxaparin Randomized assessment of Acute Coronary syndrome Treatment (INTERACT) study, combination therapy using the GP IIb/IIIa inhibitor eptifibatide (Integrilin) and the LMWH enoxaparin (Lovenox) in patients with high-risk non-ST-segment elevation ACS, resulted in improved outcomes compared to the currently recommended therapy of UF heparin, with better safety results. It is anticipated that the LMWHs may soon replace the traditional UF heparin for combination therapy with GP IIb/IIIa inhibitors in the medical stabilisation of patients with ACS. Results of other ongoing studies of LMWH combinations with other GP IIb/IIIa inhibitors and in the setting of percutaneous coronary intervention are awaited.     

The role of eptifibatide in patients undergoing percutaneous coronary intervention

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. They have been extensively studied in patients undergoing percutaneous coronary intervention (PCI). Eptifibatide, one of the approved GP IIb/IIIa inhibitors, is a small heptapeptide that is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical studies, concomitant administration of eptifibatide in patients undergoing elective PCI reduced thrombotic complications in the IMPACT-II (Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II) and ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) trials. In the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, which included 10,948 patients with non-ST-elevation acute coronary syndromes, eptifibatide significantly reduced the primary end point of death and non-fatal myocardial infarction at 30 days compared with placebo. In patients with ST-segment elevation myocardial infarction (STEMI), eptifibatide has been studied as adjunct to primary PCI and improved epicardial flow and tissue reperfusion. Studies are now evaluating eptifibatide in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS) and a planned early invasive strategy in the EARLY-ACS (Eptifibatide Administration prior to Diagnostic Catherization and Revascularization to Limit Myocardial Necrosis in Acute Coronary Syndrome) trial and in patients with primary PCI for STEMI in comparison to abciximab in the EVA-AMI (Eptifibatide versus Abciximab in Primary PCI for Acute Myocardial Infarction) trial. After the completion of these trials, the value of eptifibatide in patients undergoing PCI in different indications can be determined.     

Optimal use of platelet glycoprotein IIb/IIIa receptor antagonists in patients undergoing percutaneous coronary interventions

Discovery of the central role of platelets in the pathogenesis of acute coronary syndromes (ACS) and ischaemic complications of percutaneous coronary interventions (PCI) has led to the widespread use of oral and parenteral platelet inhibitors to treat these conditions. Glycoprotein (GP) IIb/IIIa (also known as α(IIb)β(3)) receptors on the surface of platelets play an essential role in platelet aggregation and serve as a key mediator in the formation of arterial thrombus. When activated, GP IIb/IIIa receptors bind to fibrinogen, which serves as the 'final common pathway' in platelet aggregation. Of the numerous agents developed for modulating platelet activity, intravenous platelet GP IIb/IIIa receptor antagonists are the most potent. There are four agents in clinical use, including abciximab, eptifibatide, tirofiban and lamifiban, although lamifiban is not approved for use in the US. While all agents block fibrinogen binding to GP IIb/IIIa, they do so by different mechanisms. Abciximab is a humanized form of a murine monoclonal antibody directed against GP IIb/IIIa, eptifibatide is a synthetic, cyclic heptapeptide that contains a lysine-glycine-aspartic acid (KGD) sequence that mimics the arginine-glycine-aspartic acid (RGD) sequence found on GP IIb/IIIa, tirofiban is a non-peptide antagonist derived by optimization of the tyrosine analogue that structurally mimicks the RGD-containing loop of the disintegrin echistatin, and lamifiban is a synthetic, non-cyclic, non-peptide, low-molecular-weight compound. In clinical trials, use of these agents reduces ischaemic adverse cardiovascular events in patients with ACS undergoing PCI, but at a cost of increased bleeding.     

The therapeutic use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes

Acute coronary syndrome (ACS) embraces the clinical diagnoses of unstable angina and non-Q-wave myocardial infarction (NON-Q-MI). Conventional treatment for these conditions with aspirin, heparin and other anti-anginal drugs has its limitations. Treatment of acute symptoms with lytic therapy has not been beneficial. A large proportion of patients in this high-risk group will eventually need revascularisation due to ongoing symptoms. Platelet aggregation plays a crucial role in the pathogenesis of ACS and ischaemic complications of coronary intervention. The glycoprotein (GP) IIb/IIIa receptor, which belongs to a family of surface receptors called integrins, is the final step in this pathway. This has led to the development and use of GP IIb/IIIa inhibitors as potential therapeutic agents. Inhibitors developed so far include abciximab, a chimeric monoclonal antibody, and more recently, novel synthetic intravenous and orally administered competitive integrin blocking agents. To date, abciximab, tirofiban and eptifibatide are commercially available for clinical use. Completed clinical trials have looked at these agents as a primary treatment and as an adjunct to intervention for ACS; they have shown improvement over existing treatments, with reductions in the incidence of death, myocardial infarction (MI), refractory ischaemia and need for urgent revascularisation. Risk of bleeding and thrombocytopenia is low, and appears to be dose related and associated with concomitant treatment with high dose heparin. Cost benefit has been proven.     

GP IIb/IIIa blockade in elective percutaneous coronary intervention

Cumulative scientific evidence gathered over the past ten years has confirmed the role of platelet GP IIb/IIIa inhibitors in reducing ischemic complications of patients undergoing percutaneous coronary intervention (PCI). Recently, mortality data available on more than 20,000 patients enrolled in randomized clinical trials suggest that GP IIb/IIIa blockade also improves short and long-term survival after PCI. Despite convincing arguments, GP IIb/IIIa inhibitors are still inconsistently administered in patients undergoing coronary intervention. The following review will discuss the scientific grounds and the principal controversies surrounding the use of these compounds in patients undergoing elective percutaneous coronary intervention.     

Intravenous glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: lessons from recently conducted randomized clinical trials

The opportunity to completely inhibit platelet aggregation via the glycoprotein (GP)IIb/IIIa receptor represents a major innovation in antiplatelet therapy. Numerous trials conducted during the 1990s in patients undergoing percutaneous coronary intervention established GPIIb/IIIa inhibitors as a valuable component of treatment. Phase II trials in the medical management of acute coronary syndrome (ACS) patients also suggested beneficial effects, which encouraged six major phase III clinical trials to be conducted. In general, cardiac complications were reduced in those ACS patients who were not routinely scheduled for early revascularization. However, the treatment effect in the average patient is modest and overall 100 patients need to be treated in order to prevent one death or myocardial infarction. Given the current attention to healthcare costs, these agents may therefore be reserved for patients at suspected high risk of death or (re)infarction, including patients with diabetes mellitus and elevated cardiac troponins.     

Current strategies with eptifibatide and other antiplatelet agents in percutaneous coronary intervention and acute coronary syndromes

Antiplatelet and anticoagulation therapies are essential for the prevention of thromboembolic-induced myocardial ischaemia in non-ST-elevation acute coronary syndromes and the ischaemic complications of percutaneous coronary intervention. Although heparin, direct thrombin inhibitors and oral platelet activation inhibitors provide substantial benefit, only glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway leading to platelet aggregation, and the American College of Cardiology/American Heart Association guidelines recommend GP IIb/IIIa inhibitors as an integral component of care in these patients. Abciximab, eptifibatide and tirofiban all act through the GP IIb/IIIa receptor; however, variations in clinical outcomes among patients receiving these agents may be related to their structural and pharmacological differences, as well as to patient demographics. Data indicate that eptifibatide, at the current recommended dosing schedule, achieves the highest level of consistent platelet inhibition compared with current doses of abciximab and tirofiban.     

The chimeric monoclonal antibody abciximab: a systematic review of its safety in contemporary practice

Background: Abciximab is a monoclonal antibody that prevents platelet aggregation by blocking platelet glycoprotein (GP) IIb/IIIa receptor. Objective: To study the safety profile of this agent in contemporary clinical practice. Methods: We evaluated efficacy and safety end points (major and minor bleeding, thrombocytopenia) in patients treated with abciximab and compared them to those treated with placebo in main randomized clinical trials of patients with acute coronary syndromes (ACS) or those undergoing percutaneous coronary intervention (PCI). Results/conclusion: Use of abciximab is associated with an improved outcome in high-risk patients undergoing PCI but with a worse outcome in ACS patients treated conservatively. Use of abciximab is associated with an acceptable safety profile even when used on a background of aspirin and high doses of thienopyridine but has a potential to increase thrombocytopenia and minor bleeding. Small molecule GP IIb/IIIa antagonists are increasingly preferred over abciximab in clinical practice, and recent observational data have demonstrated these agents to have a similar efficacy and safety profile. As an increasing number of agents are being evaluated for peri-PCI anti-thrombotic therapy, the role of abciximab is likely to be further restricted to the highest risk patients.     

The role of eptifibatide in patients undergoing percutaneous coronary intervention

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. They have been extensively studied in patients undergoing percutaneous coronary intervention (PCI). Eptifibatide, one of the approved GP IIb/IIIa inhibitors, is a small heptapeptide that is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical studies, concomitant administration of eptifibatide in patients undergoing elective PCI reduced thrombotic complications in the IMPACT-II (Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II) and ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) trials. In the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, which included 10,948 patients with non-ST-elevation acute coronary syndromes, eptifibatide significantly reduced the primary end point of death and non-fatal myocardial infarction at 30 days compared with placebo. In patients with ST-segment elevation myocardial infarction (STEMI), eptifibatide has been studied as adjunct to primary PCI and improved epicardial flow and tissue reperfusion. Studies are now evaluating eptifibatide in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS) and a planned early invasive strategy in the EARLY-ACS (Eptifibatide Administration prior to Diagnostic Catherization and Revascularization to Limit Myocardial Necrosis in Acute Coronary Syndrome) trial and in patients with primary PCI for STEMI in comparison to abciximab in the EVA-AMI (Eptifibatide versus Abciximab in Primary PCI for Acute Myocardial Infarction) trial. After the completion of these trials, the value of etifibatide in patients undergoing PCI in different indications can be determined.     

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In clinical trials in patients with acute or unstable coronary syndromes and/or undergoing percutaneous coronary intervention, oral glycoprotein (GP) IIb/IIIa antagonists did not show therapeutic benefit over aspirin during long-term administration. Moreover, high-dose oral administration of these agents was associated with greater fatality risk compared with that of lower doses. This article postulates that continuous exposure of the GP IIb/IIIa receptor (integrin αIIbβ₃) to these agents may result in some form of resistance or activation of other biological systems. These toxicological mechanisms may help explain some factors that could potentially contribute to the failure of these agents in clinical trials. Several hypotheses are presented: (i) modulation of platelet response because of long-term exposure to GP IIb/IIIa antagonists; (ii) role of related integrins and associated proteins to compensate for the loss of platelet activity because of dysfunctional GP IIb/IIIa receptors occupied by inhibitors; (iii) effects of the GP IIb/IIIa antagonists on other cellular systems such as the caspase and procaspase enzymes in apoptosis and possibly the ryanodine receptor involved in sarcoplasmic reticulum calcium release. These toxicological mechanisms could potentially limit the utility of these oral agents in long-term administration.     

Interventional Cardiovascular Pharmacotherapy

In the last decade, a variety of novel anticoagulant and antiplatelet agents that improve outcomes in patients undergoing percutaneous coronary revascularization have emerged. During the next decade, continued refinements in catheter-based device technology should lead to further increases in the number of interventional procedures. The use of optimal antithrombotic strategies is pivotal in reducing adverse events among patients undergoing percutaneous coronary intervention (PCI). Our purpose is to review the current evidence regarding the efficacy of available adjunctive anticoagulant and antiplatelet agents in treating patients undergoing percutaneous coronary revascularization. It should be borne in mind that patients undergoing PCI in the midst of an acute coronary event require a different level of coagulation and platelet aggregation inhibition than low-risk patients undergoing elective PCI for stable angina pectoris. Similarly, generalizing antithrombotic regimen safety data to a wide spectrum of catheter-based therapeutic devices should be avoided. A level of anticoagulation that is safe and effective for angioplasty and stent placement may not be sufficient for devices with longer intracoronary dwell times such as brachytherapy catheters. In light of current evidence, activated clotting times should be targeted in the 200- to 250-second range during elective PCI and in the 250- to 300-second range when intervening on a higher-risk lesion, such as one with an angiographically visible thrombus or in patients presenting with an acute coronary syndrome (ACS).Low-dose enoxaparin sodium is an attractive antithrombin strategy in PCI because it is intrinsically adjusted for renal function, age, and concomitant glycoprotein (GP) IIb/IIIa antagonist use. Other low-molecular weight heparins have also been studied as adjunctive anticoagulants during cardiac catheterization. For example, in pilot studies, dalteparin sodium was shown to have a good safety profile when used alone or in combination with abciximab during PCI.A wealth of data supports the use of a GP IIb/IIIa antagonist in patients presenting with ACS, especially those with high-risk features such as elevated cardiac markers; the systematic use of GP IIb/IIIa inhibitors in this population is therefore encouraged. Overall, the use of GP IIb/IIIa inhibitors reduces the incidence of thrombotic complications following PCI, is associated with a mortality benefit, but has no impact on the risk of restenosis.     

Costs and cost effectiveness of low molecular weight heparins and platelet glycoprotein IIb/IIIa inhibitors: in the management of acute coronary syndromes

The most well established antithrombotic treatment for acute coronary syndromes (ACS) is unfractionated heparin (UFH) plus aspirin, but such treatment may not prevent arterial thrombotic events. Low molecular weight heparins (LMWHs) and platelet glycoprotein (GP) IIb/IIIa inhibitors offer alternative or adjunctive treatments. However, before these alternatives with higher acquisition costs are accepted in today's healthcare systems, their cost effectiveness must be proven. This paper reviews international pharmacoeconomic studies on the use of LMWHs and GP IIb/IIIa inhibitors in patients with ACS in an attempt to determine whether these therapies are cost effective. Most of the studies on LMWHs have been cost-minimisation analyses and have focused on enoxaparin sodium, because this is the only LMWH proven to be superior to UFH. Several analyses show that, compared with UFH plus aspirin, enoxaparin sodium provides cost savings both during hospitalisation (30 days) and 1-year follow-up. These cost savings are mainly attributable to fewer cardiac interventions, shorter hospital stays and lower administrative costs. Indeed, the clinical and economic advantages of enoxaparin sodium have led to its recommendation in recent guidelines as the antithrombotic agent of choice for coronary artery disease. Most of the economic analyses of GP IIb/IIIa inhibitors have been cost-effectiveness analyses. Such analyses indicate that the high acquisition costs of these drugs may be at least partially offset by reductions in other costs if a noninvasive approach to risk stratification is used. Furthermore, use of GP IIb/IIIa inhibitors appears to give favourable cost-effectiveness ratios compared with other accepted therapies, such as fibrin-specific thrombolytic therapy, in the cardiovascular field, particularly in high-risk patients and those undergoing percutaneous coronary intervention. However, more comprehensive economic data on the GP IIb/IIIa inhibitors are needed.     

Eptifibatide: a review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention

Eptifibatide (Integrilin) is a highly specific, reversible, intravenously administered glycoprotein (GP) IIb/IIIa receptor antagonist that acts at the final common step of the platelet aggregation pathway. Data from large clinical trials indicate that intravenous eptifibatide as adjunctive therapy to standard care is effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI). In the ESPRIT (Enhanced Suppression of the Platelet glycoprotein IIb/IIIa Receptor with Integrilin Therapy) trial in patients undergoing PCI with stenting, eptifibatide, compared with placebo, achieved significant reductions in death and ischaemic complications and was better than a strategy of reserving treatment for the bailout situation. In the large PURSUIT (Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial in patients with NSTE ACS, eptifibatide was associated with a significant reduction in the incidence of death or myocardial infarction (MI) compared with placebo. Eptifibatide is well tolerated in these trials. Ongoing trials are currently investigating the efficacy and tolerability of regimens that include this agent in other indications, including ST-segment elevation MI (STEMI).     

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The success of intravenous platelet glycoprotein (GP) IIb/IIIa receptor blockers as potent antithrombotic therapies has ignited interest in the research and development of oral agents with the intention of extending the initial clinical benefits proven with intravenous GP IIb/IIIa blockers to long-term care with the use of oral agents. Nonetheless, results of the recently published Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial support the disappointing results of the earlier published studies, which revealed that the use of oral GP IIb/IIIa inhibitors was associated with an unacceptable increased mortality. Further research to elucidate the mechanism of this increased fatality risk is warranted before any further clinical studies with the oral GP IIb/IIIa inhibitors can be ethically justified.     

Eptifibatide: a potent inhibitor of the platelet receptor integrin glycoprotein IIb/IIIa

The platelet glycoprotein (GP) IIb/IIIa integrin plays a key role in mediating platelet aggregation. Blockade of the platelet GP IIb/IIIa receptor prevents arterial thrombosis in animal models much better than does aspirin. Among the most specific inhibitors in this class of drugs is eptifibatide (Integrilin^TMMillennium Pharmaceuticals, Inc.), a cyclic heptapeptide based on a peptide recognition sequence found in snake venom. Peptide inhibitors, such as eptifibatide, bind competitively to GP IIb/IIIa and have a short half-life, allowing the effect to be rapidly reversible and providing a favourable overall safety profile. Eptifibatide has been studied in a broad range of ischaemic coronary conditions including percutaneous coronary intervention (PCI), ST-segment and non-ST-segment acute myocardial infarction (MI) and unstable angina. In PCI and non-ST-segment MI, therapy with eptifibatide has been shown to reduce acute ischaemic complications without any increased risk of life-threatening adverse events. In the recently reported Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, two 180 μg/kg boluses of eptifibatide, 10 min apart, followed by an 18 – 24 h infusion at 2 μg/kg/min given as adjunctive therapy in non-urgent PCI reduced the 30-day composite of death, MI and need for urgent target vessel revascularisation from 10.4 to 6.8% compared with placebo. These results were achieved under conditions of typical contemporary PCI, namely the implantation of second- and third-generation stents deployed at high balloon pressures along with modern adjunctive pharmacological treatment, particularly the universal use of thienopyridines and lower-dose heparin. Few significant pharmacological effects other than inhibition of platelet aggregation and the effect on bleeding time have been reported. Future research will focus on alternative clinical applications and combinations with other therapies to further improve cardiovascular outcomes.