Synthetic inhibitors of platelet glycoprotein IIb/IIIa in clinical development

Activation of the platelet glycoprotein (GP IIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of GP IIb/IIIa receptors include monoclonal antibodies (abciximab) against this receptor and peptidic and nonpeptidic synthetic specific receptor blockers. Abciximab exchanges between and binds to platelets for as long as 2 weeks, whereas synthetic GP IIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion, but some have the advantage of also being orally active. In the secondary prevention of atherothrombosis, large-scale trials were successfully conducted with aspirin, dipyridamole, ticlopidine, and clopidogrel. In the first large-scale trials with GP IIb/IIIa inhibitors, abciximab was investigated. In aggregate, synthetic GP IIb/IIIa inhibitors, combined with aspirin and heparin, were shown to reduce ischemic events in patients with high- and low-risk coronary intervention, stents, unstable angina, and non-Q-wave infarction. With short-term use of synthetic GP IIb/IIIa inhibitors, there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses currently used, bleeding occurs more often with the synthetic GP IIb/IIIa inhibitors (used for 3 days) than with abciximab (used for 12 hours), but there are no direct comparisons between these drugs.     

Relation of local platelet glycoprotein IIb/IIIa independent activation during coronary angioplasty in acute myocardial infarction to recovery of left ventricular function

We assessed glycoprotein (GP) IIb/IIIa independent platelet activation in coronary sinus and peripheral blood from patients who underwent angioplasty for acute myocardial infarction and stable angina. Despite complete blockade of the activated GP IIb/IIIa receptor with abciximab in patients with acute myocardial infarction, unsuppressed local GP IIb/IIIa independent activation was associated with a lack of recovery of left ventricular function.     

Clinical trials of glycoprotein IIb/IIIa inhibitors

Glycoprotein (GP) IIb/IIIa inhibitors were developed to block platelet aggregation and potentially to abolish thrombus formation. Clinical trials have demonstrated that GP IIb/IIIa inhibitors are more potent antithrombotic agents than aspirin and heparin alone. GP IIb/IIIa inhibitors reduce short- and long-term complications of percutaneous revascularization. These agents also are effective as adjuncts to various treatment strategies for the management of patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQMI). Furthermore, recent clinical trials with a small number of patients suggest that GP IIb/IIIa inhibitors in combination with low-dose fibrinolytics are safe and effective for the treatment of ST segment elevation myocardial infarction. The clinical trials of GP IIb/IIIa inhibitors summarized here examined different patient populations managed under different strategies. Moreover, these agents have different indications for clinical use and varying safety profiles.     

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.     

Effects of enoxaparin and nadroparin on major cardiac events in high-risk unstable angina treated with a glycoprotein IIb/IIIa inhibitor

Clinical trials have reported the beneficial effects of platelet glycoprotein (GP) IIb/IIIa receptor antagonists and low-molecular-weight heparins (LMWH) on major cardiac events (MACE) in patients presenting with unstable angina or non-ST elevation myocardial infarction. A number of studies have documented the significant superiority of low-molecular-weight heparins, especially enoxaparin, over unfractionated heparin in the treatment of acute coronary syndromes. The purpose of this study was to compare the effects of two different LMWHs, enoxaparin and nadroparin, accompanied by platelet GP IIb/IIIa inhibition on MACE in high-risk unstable angina. The study was designed as an open-label and observational study. Sixty-eight patients presenting with unstable angina associated with high-risk criteria were randomly assigned to treatment with enoxaparin plus tirofiban (36 patients, mean age 57 +/- 11) or nadroparin plus tirofiban (32 patients, mean age: 58 +/- 8). In-hospital MACE including acute myocardial infarction (AMI), recurrent refractory angina, death, stroke, and urgent revascularization were compared between the study groups. Patient characteristics and durations of LMWH and tirofiban treatments were not different between the study groups. Coronary artery risk factors, except family history (which was observed more frequently in the enoxaparin group, P = 0.02), were also similar. MACE between the enoxaparin and nadroparin groups including AMI (5.5%, 6%), recurrent refractory angina (19%, 12%), death (0%, 3%), stroke (was not observed in either group), urgent revascularization (14%, 12%) and total MACE (19%, 15%) were not different. Enoxaparin and nadroparin, accompanied by GP IIb/IIIa inhibitor therapy, have similar effects on the development of major cardiac events in patients presenting with unstable angina and high-risk characteristics.     

Antithrombotic therapy in the acute phase of unstable angina

Low molecular weight heparins appear to be a better choice in patients with unstable angina than unfractionated heparin. In addition, the excellent predictable dose-response makes them suitable to prevent ischemic complications of percutaneous coronary intervention. Although direct comparisons between LMWH and UH are limited, substantial evidence exists that patients receiving LMWH can be safely brought to cardiac catheterization. Therefore, previous concern regarding transitioning such therapy from the medical service to the cardiac catheterization laboratory should not impede the upstream use of thèse agents. Although UH remains an option in conjunction with GP IIB/IIIa inhibitors, there is substantial evidence that LMWH and GP IIb/IIIa inhibitor therapy can be used safely in combination. Although GP IIb/IIIa inhibitors are very potent to prevent ischemic events after percutaneous coronary interventions, their benefit in the medical management of unstable angina is much more modest. ADP receptor antagonists reduce major ischemic events in combination with aspirin in the medical management of unstable angina patients but also when PCI is planned. Their combination with GP IIB/IIIa receptor antagonist does not impair the benefit of GP IIb/IIIa antagonists. The development of biologic tools to monitor these antithrombotic regimen is highly warranted especially in high risk patients (chronic renal failure, elderly).     

Noncardiac applications of glycoprotein IIb/IIIa inhibitors

Platelet activation and aggregation have become increasingly recognized as the primary processes involved in the cascade that leads to thrombus formation in atherosclerotic vascular disease. Glycoprotein IIb/IIIa receptor inhibitors (GPI) favorably impact thrombus formation and distal embolization by inhibiting the final common pathway of platelet aggregation. Glycoprotein IIb/IIIa inhibitors have been used effectively in a wide variety of clinical scenarios including unstable angina, non‐ST segment elevation myocardial infarction, ST segment elevation myocardial infarction, and low and high risk percutaneous coronary interventions with and without intracoronary stenting, however there is limited data regarding the use of these potent antiplatelet agents in the setting of extracardiac vascular disease. This article will review the non‐cardiac applications of glycoprotein IIb/IIIa inhibitors in the setting of acute ischemic stroke, carotid and vertebral angioplasty and stenting, acute critical limb ischemia, and percutaneous interventions in peripheral arterial occlusive disease. Catheter Cardiovasc Interv 2004;62:530–538. © 2004 Wiley‐Liss, Inc.     

Combination antiplatelet treatment in coronary artery disease patients: A necessary evil or an overzealous practice?

In seeking to improve care in coronary artery disease patients, further platelet inhibition has been occasionally applied beyond that provided by aspirin and a P2Y₁₂ receptor antagonist. This review aims to offer insights about the rationale, the efficacy and safety of combination antiplatelet therapy, involving three or more agents. Overall, the use of glycoprotein (GP) IIb/IIIa inhibitors did not significantly modify the treatment effect of different antiplatelet strategies, including double vs standard clopidogrel, prasugrel vs clopidogrel, ticagrelor vs clopidogrel, cangrelor vs clopidogrel, and vorapaxar vs placebo. With the caveat that the use of GP IIb/IIIa inhibitor was not randomized, adding such an agent to aspirin and a P2Y₁₂ receptor antagonist appears to carry a significantly increased bleeding potential. Moreover, adding vorapaxar to aspirin- and clopidogrel-treated patients is associated with more bleeding events, while the bleeding potential is further exacerbated in cases of quadruplicate antiplatelet treatment including aspirin, clopidogrel, vorapaxar, and a GP IIb/IIIa inhibitor. In ST-segment elevation, myocardial infarction patients’ administration of an intravenous antiplatelet agent (GP IIb/IIIa inhibitor or cangrelor), in addition to aspirin and a P2Y₁₂ receptor antagonist, efficiently bridges the pharmacodynamic gap of oral agents. Cilostazol on top of aspirin and clopidogrel appears to be safe, although of questionable clinical benefit. In conclusion, combination antiplatelet therapy should be reserved only for selected cases and following thoughtful consideration of the associated risk/benefit ratio.     

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.     

Increased platelet aggregation induced activity by anti-glycoprotein IIb/IIIa antibody in patients with acute coronary syndrome

Interaction of glycoprotein (GP) IIb/IIIa with fibrinogen is the final and key reaction in platelet aggregation. In order to evaluate GP IIb-IIIa functional activity in patients with acute coronary syndrome (ACS) we measured platelet aggregation induced by monoclonal antibody CRC54 which is directed against GP IIb/IIIa and is able to stimulate its binding with fibrinogen and subsequent aggregation. Patients with ACS were divided into 3 groups: (1) with Q-wave myocardial infarction (MI), (2) with non Q-wave MI and with unstable angina. Patients with stable angina (SA) and healthy donors formed 2 comparison groups. The level and rate of CRC54-induced aggregation measured both in the absence and in the presence of prostaglandin E(1) (PGE(1)), the inhibitor of platelet activation, in all groups of patients with ACS were > or =1.5 times higher than in SA patients and healthy donors. Observed differences in the parameters of CRC54-induced aggregation at least in the presence of PGE(1) could be caused only by increased GP IIb/IIIa fibrinogen binding ability in ACS patients, but not by differences in the level of platelet activation. In all groups of patients with ACS, but not in SA patients and healthy donors, strong correlation (r=-0.5-0.7) was observed between increased parameters of ADP-induced aggregation and aggregation stimulated by CRC54 in the presence of PGE(1). The data obtained indicated that increased of platelet aggregating capacity in ACS might be caused by changes of GP IIb/IIIa functional characteristics and not by enhancement of platelet sensitivity towards physiological agonists including ADP.     

Treatment of unstable angina: the role of platelet inhibitors and anticoagulants

Thrombo-occlusive events at sites of atherosclerotic stenosis and plaque rupture are caused by exposure of the sub-endothelial layer of the vasculature to platelets and their subsequent aggregation at the locus of injury. Thrombi are generated by the activation of platelets, which are not always inhibited by aspirin or heparin. Both unstable angina and myocardial infarction are ultimately linked to thrombus formation. In addition, various invasive procedures used to re-establish patency of coronary vessels are often followed by thrombotic events that can be life threatening. New antagonists to thrombin and the development of glycoprotein (GP) IIb/IIIa platelet receptor inhibitors have been the main focus of recent large clinical trials that have demonstrated both the efficacy and safety of these new agents. The new antithrombotics include hirudin, hirulog, and the low molecular weight heparins. Representative GP IIb/IIIa receptor blockers include: abciximab, a human-murine chimeric monoclonal antibody; tirofiban, a non-peptide tyrosine derivative with a short half-life; and eptifibatide, a cyclic heptapeptide. All three are available for clinical use, but their approved indications vary. The GP IIb/IIIa receptor antagonists are anticipated to gain wide clinical acceptance by both cardiologists and internists and should have a prominent role in the management of acute coronary syndromes, most likely in combination with an antithrombin.     

Progress in the field of GPIIb/IIIa antagonists

Platelet aggregation plays an important role in pathological situations such as myocardial infarction, unstable angina, peripheral artery disease, and stroke. Thus, pharmacological agents that specifically inhibit platelet aggregation are of great interest in the treatment and prevention of these cardiovascular diseases. Since binding of activated glycoprotein IIb/IIIa complex, a platelet surface integrin, to fibrinogen is the final step leading to platelet aggregation regardless of the initial stimulus, many researches have focused on the development of drugs that could antagonize this integrin. Three intravenous glycoprotein IIb/IIIa antagonists are currently marketed for the prevention of myocardial infarction in patients undergoing percutaneous intervention: Abciximab, Eptifibatide and Tirofiban. To further test the clinical efficacy of these agents, oral glycoprotein IIb/IIIa antagonists have been developed but only led to disappointing clinical results. Nevertheless, due to recognized usefulness of oral agents for the prevention and treatment of cardiovascular diseases, a great number of new orally active compounds are under clinical or preclinical evaluation. The aim of this review is to describe the chemical, pharmacological and clinical properties of existing and forthcoming glycoprotein IIb/IIIa antagonists.     

A propensity analysis of the impact of platelet glycoprotein IIb/IIIa inhibitor therapy on in-hospital outcomes after percutaneous coronary intervention

It is unknown whether the benefits of parenteral platelet glycoprotein (GP) IIb/IIIa inhibitors as an adjunct to percutaneous coronary intervention (PCI) demonstrated in randomized clinical trials extend to patients treated outside the setting of clinical trials. A contemporary registry of 10,847 consecutive PCI procedures was analyzed to determine the effect of GP IIb/IIIa inhibitor treatment on in-hospital major adverse coronary events ([MACEs] composite of death, urgent coronary artery bypass surgery, periprocedural myocardial infarction, abrupt closure, and stent thrombosis). In this registry, GP IIb/IIIa inhibitors were administered to 20.1% of patients. These patients were younger, more often men, and less often hypertensive than untreated patients. GP IIb/IIIa inhibitor-treated patients were more likely to present with acute myocardial infarction or unstable angina. Stents were placed in 79% of patients treated with GP IIb/IIIa inhibitors. MACEs occurred in 7.8% of GP IIb/IIIa inhibitor-treated patients compared with 3.8% of untreated patients (p <0.001). After multivariable adjustment for the propensity of GP IIb/IIIa inhibitor treatment as well as other possible confounders and interactions known to influence MACEs, GP IIb/IIIa inhibitor treatment was associated with a 57% increase in the risk of a MACE (odds ratio 1.57, 95% confidence interval 1.22 to 2.03; p = 0.0004). In a data set consisting of patients with a high degree of acuity predominantly treated with stent placement, GP IIb/IIIa inhibitor treatment is associated with an increase in thrombotic complications of PCI.     

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.     

Oral platelet glycoprotein IIb/IIIa inhibition

Platelet aggregation plays a central role in the pathogenesis of thrombosis and the acute coronary syndromes. When given intravenously, potent selective antagonists of fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, the final common pathway for platelet aggregation, have been effective in the treatment of acute coronary syndromes. Their benefit ceases, however, with the end of the infusion. Aspirin reduces the incidence of secondary vascular events by 25% to 30% after an acute coronary syndrome, and clopidogrel provides modest improvement over aspirin. However, both are relatively weak antiplatelet agents that each block only one of many pathways to platelet activation and surface membrane expression of the competent GP IIb/IIIa receptor. With the success of the intravenous GP IIb/IIIa antagonists in the acute setting, recent interest has focused on the potential benefit of oral GP IIb/IIIa antagonists used long-term for secondary prevention. The oral agents tested in phase III studies thus far have not performed up to expectations, however. The following paper reviews these studies and the implications of their results.     

Bleeding complications with platelet glycoprotein IIb/IIIa receptor antagonists.

Platelet glycoprotein (GP) IIb/IIIa receptor antagonists are being used with increasing frequency in the settings of percutaneous coronary interventions and acute ischemic syndromes. The development of bleeding complications following GPIIb/IIIa blockade represents a significant limitation to its effectiveness. Baseline characteristics predictive of future bleeding events in patients receiving platelet GPIIb/IIIa receptor antagonist include older age, low body weight, evolving myocardial infarction, and female sex. In patients undergoing percutaneous coronary interventions with adjunctive GPIIb/IIIa inhibition, the risk of bleeding, particularly from the femoral vascular access site, may be reduced through the use of low-dose, weight-adjusted heparin (70 U/kg), avoidance of postprocedural heparin, and early vascular sheath removal. Strategies to reduce the incidence of bleeding complications in patients receiving GPIIb/IIIa inhibitors are proposed in this article.     

Eptifibatide provides additional platelet inhibition in non-ST-elevation myocardial infarction patients already treated with aspirin and clopidogrel. Results of the platelet activity extinction in non-Q-wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study

OBJECTIVES: The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention. BACKGROUND: Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear. METHOD: Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load. RESULTS: After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion. CONCLUSIONS: The activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect.     

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.     

Glycoprotein IIb/IIIa receptor inhibitor-thrombolytic combination therapy for acute myocardial infarction

Over the past two decades, we have witnessed a large decrease in the death and complication rate of patients experiencing acute myocardial infarction (MI), due to our ability to restore blood flow to infarct-related arteries. Therapies include strategies to inhibit platelet function and induce fibrinolysis, and mechanical reperfusion with percutaneous intervention. Despite decreases in morbidity and mortality with thrombolytic therapy, reperfusion rates remain less than optimal. With standard fibrinolytic therapy in combination with aspirin, it is thought that thrombolyticinduced platelet activation may be an important reason for failure to induce perfusion, or maintain reperfusion in the infarct-related artery. In the past 10 years we have moved from platelet inhibition with aspirin to newer, more potent platelet inhibitors such as glycoprotein (GP) IIb/IIIa antagonists. Recent trials have evaluated the efficacy and safety of combining thrombolytic drugs with GP IIb/IIIa receptor antagonists. Future trends may use combination therapy as a part of a mechanical strategy, using these medications to induce early reperfusion as the patient is prepared for percutaneous intervention. This review summarizes recently published trials using combination thrombolytic and GP IIb/ IIIa receptor inhibitor therapy in the treatment of acute MI.     

Drip and Ship: A New Strategy for the Treatment of Acute Coronary Syndromes

Glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway of platelet aggregation by preventing fibrinogen from binding to the GP IIb/IIIa platelet receptor. In patients with unstable angina (UA) or a non–Q wave myocardial infarction (NQWMI), including those with UA refractory to medical therapy, these agents decrease the risk of death, myocardial infarction (MI), and recurrent ischemia. Most patients with acute coronary syndromes are managed in hospitals without on-site angioplasty capabilities and often require transfer for an interventional procedure. We propose that GP IIb/IIIa inhibitors can be safely initiated at the referring hospital. We studied 20 patients with UA/NQWMI in whom therapy with a GP IIb/IIIa inhibitor, in addition to standard medical therapy, was initiated prior to transfer for an urgent percutaneous coronary intervention (PCI) (drip and ship). The primary end point was a composite of death, MI, and recurrent ischemia at 30 days. Twelve patients were treated with abciximab, 5 patients were treated with tirofiban, and 3 patients initially treated with tirofiban were converted to abciximab. Procedural success occurred in 33 out of 36 (92%) lesions and 18 out of 20 (90%) patients. At 30 days, 4 out of 20 (20%) patients had recurrent ischemia. The PTCA sites were widely patent in the 3 patients who underwent repeat angiography. The fourth patient had an unsuccessful PCI and was referred for coronary artery bypass surgery. There were no MIs or deaths. Patients who require transfer for an urgent PCI can be managed safely and efficaciously by initiating a GP IIb/IIIa inhibitor, in addition to standard medical therapy, prior to transfer.