Eptifibatide Group Research Articles

Effects of Preoperative Abciximab and Eptifibatide on Bleeding Indices in Coronary Artery Bypass Graft Patients

Background: Glycoprotein (GP) IIb/IIIa antagonists are used routinely for the treatment of acute coronary syndrome and to prevent thromboses during percutaneous coronary interventions. It is not uncommon for patients who initially require a GP IIb/IIIa inhibitor to eventually receive a surgical intervention. Objective: To compare the difference in bleeding indices in patients who undergo coronary artery bypass grafting (CABG) after receiving either eptifibatide or abciximab. Methods: A retrospective chart review was completed on all adults who received abciximab or eptifibatide within 24 hours prior to undergoing CABG. Patients were excluded if they had received a dose of warfarin within 96 hours prior to the procedure or if they had an incomplete medical record, an off-pump procedure, a known hypercoagulable disorder, or hemophilia. A total of 54 patients were included and preoperative data, including doses of anticoagulant and antiplatelet agents, were recorded. Intraoperative and postoperative data collected for analysis included hemoglobin level, chest tube output, and the amount of blood products transfused for 24 hours postprocedure. Results: There was a statistically significant difference between the eptifibatide and abciximab groups in the amount of fresh frozen plasma (mean ± SD, 21 ± 31 vs 187 ± 125 mL, respectively; p < 0.05) and platelets (212 ± 81 vs 433 ± 118 mL, respectively; p < 0.01) transfused during the intraoperative period. However, when the total amount of blood products transfused intraoperatively (769 ± 243 vs 1395 ± 316 mL, respectively; p = 0.47) was evaluated, no significant difference was detected. Likewise, markers for bleeding that were collected during the 24-hour postoperative window (immediate and 24-h postoperative hemoglobin and total 24-h chest tube output) were not significantly different. Conclusions: Although there is an increased risk of bleeding when abciximab or eptifibatide is administered prior to CABG, no significant difference in the total amount of blood products used was detected between the 2 agents in this study.

A randomised controlled trial of upstream administration of eptifibatide in patients presenting non-ST segment elevation acute coronary syndrome treated with an invasive strategy

To prospectively evaluate the benefit of upstream administration of eptifibatide in patients with non ST-segment elevation acute coronary syndrome (NSTEACS) pretreated with aspirin and clopidogrel. The PRACTICE study was an international, randomised, multicentre trial of 393 patients (of 766 planned) who presented with NSTEACS. Patients were randomly assigned to double-blind treatment with eptifibatide (n=196) or placebo (n=197). Investigators used aspirin, clopidogrel with a loading dose of 300 mg followed by a daily dose of 75 mg, and heparin (unfractionated or low molecular weight) in both groups. An invasive strategy was planned within 6 to 48 hours. The primary endpoint was a composite of death, myocardial infarction, or urgent revascularisation at 30 days. The primary end point occurred in 31 patients (15.8%) in the eptifibatide group and in 33 patients (16.8%) in the placebo group (odds ratio 0.93, 95 percent confidence interval 0.53 to 1.53, P=0.70). The overall incidence of bleeding was not significantly different in the eptifibatide and the placebo groups (14.4% vs 11.3%, p=0.35). We did not find a measurable benefit of upstream administration of eptifibatide on top of aspirin and clopidogrel in patients presenting with NSTEACS managed by an invasive strategy. Further studies are warranted to further evaluate the clinical benefit of upstream eptifibatide in patients pretreated by clopidogrel in a larger population.

Unfractionated Heparin Reduces the Anti-Platelet Effects of Abciximab but not Eptifibatide During PCI

In 29 patients undergoing percutaneous coronary intervention (PCI), we obtained blood samples at baseline, 10 minutes after standard weight-based abciximab (n=15) or double-bolus eptifibatide (n=14) and 5 minutes after unfractionated heparin (UFH; 70 U/kg bolus). The median percent inhibition was significantly higher in the eptifibatide group compared with the abciximab group both before (96.5% [94-100] vs. 85% [77-89.5] [adenosine diphosphate; ADP]; 89.5% [84-95] vs. 59% [37.5-76.5] [thrombin receptor agonist peptide; TRAP], p<0.001 for both) and after UFH (95% [93-100] vs. 79% [68.8-87.5] [ADP]; 82% [77-93] vs. 51% [34.5-71.3] [TRAP], p<0.001 for both). Addition of UFH significantly reduced platelet inhibition in the abciximab group (85% [77-89.5] vs. 79% [68.8-87.5] [ADP]; 59% [37.5-76.5] vs. 51% [34.5-71.3] [TRAP], p<0.05 for both) but not in the eptifibatide group (96.5% [94-100] vs. 95% [93-100] [ADP]; 89.5% [84-95] vs. 82% [77-93] [TRAP], p=ns for both). Eptifibatide achieved superior platelet inhibition before but especially after UFH compared with abciximab.

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.

Anticoagulant and antiplatelet medications

In the article, “Non–ST-Segment Elevation Acute Coronary Syndromes: Management Strategies for Optimal Outcomes” (February 2006[suppl]: S8-S34), Susan Housholder-Hughes presents a very good, broad overview of many facets of this syndrome and its management. However, there is some information on anticoagulant and antiplatelet medications that I feel may be misleading and benefit from further clarification.On page 23, it is stated that direct thrombin inhibitors do not require monitoring; however, they do. Argatroban, lepirudin, and hirudin all must be closely monitored by partial thromboplastin time (PTT) as often as every 2 hours to ensure appropriate dosing. With argatroban, PTT should be checked 2 hours after initiation of the infusion, and 2 hours after any change, then can be decreased to twice daily if at goal range. For lepirudin and hirudin, PTT should be checked 4 hours after initiation or change, then can be decreased to daily if at goal range. Also, because argatroban is cleared hepatically, the starting infusion rate should be lower than the 2.0 μg/kg/min noted if there is any hepatic impairment.Lepirudin and hirudin are cleared renally and dose adjustments are also necessary. Bivalirudin (more commonly used during percutaneous interventions) should have associated activated clotting time monitoring, if there is any renal impairment.The issue of thrombocytopenia resulting from use of some glycoprotein IIb-IIIa receptor inhibitors is reviewed; however, it is not noted that a baseline platelet count of under 100000 is a contraindication to using any of these agents. It is also stated (page 24) that eptifibitide “has not been associated with increased rates of thrombocytopenia vs placebo,” with reference given to the PURSUIT trial experience in 1999.1 While realizing that the article was written in 2004, a review of more recent references since 1999 would have been helpful to show how more recent clinical experiences have added to the side effect profile of the drug. Although thrombocytopenia appears to be less common with eptifibatide, there have been several reports of severe thrombocytopenia associated with eptifibatide,2–5 and myself and my colleagues have experienced this clinically many times as well.The comments about the need for monitoring of direct thrombin inhibitors and the contraindication to use of glycoprotein IIb-IIIa inhibitors in patients with a platelet count of less than 100000/mL are valid and accurate, and I thank Ms Chevoya for this clarification.As for the lack of increase in thrombocytopenia with eptifibatide versus placebo, the prescribing information for INTEGRILIN (eptifibatide) states that the rates of thrombocytopenia in the PURSUIT trial with eptifibatide and placebo were similar. As reported by McClure and colleagues,1the rates of thrombocytopenia (defined as platelet count<100000/mL or <50% of baseline) in the PURSUIT trial were 7% (319/4603) in the placebo group and 6.9% (314/4614) in the eptifibatide group, demonstrating that eptifibatide is not associated with increased incidence of thrombocytopenia versus placebo. Randomized, placebo-controlled clinical trials, such as PURSUIT, provide the most reliable scientific evidence regarding the prevalence of relatively infrequent events, such as thrombocytopenia, while also allowing the comparison of individual event rates with the active drug versus placebo. Although individual cases of severe thrombocytopenia in patients receiving eptifibatide have been reported in the literature, as noted by Ms Chevoya, it is unclear whether thrombocytopenia is directly related to the use of this drug in these cases. Additionally, these case reports do not have a control group, in contrast to randomized, placebo-controlled trials. Finally, treatment with eptifibatide, including readministration within 28 days, has not been associated with development of antibodies to eptifibatide (as described in the INTEGRILIN prescribing information), a finding that is consistent with the absence of increased thrombocytopenia with eptifibatide versus placebo in the PURSUIT trial. Therefore, in my opinion, the statement “eptifibatide has not been associated with increased rates of thrombocytopenia vs placebo” is still accurate and valid.

Anti-thrombotic effect of bivalirudin compared with eptifibatide and unfractionated heparin in diabetic patients

Patients with diabetes who undergo percutaneous coronary intervention (PCI) are at high risk for thrombotic complications following the procedure. We sought to compare the anti-thrombotic effect of bivalirudin to that of eptifibatide plus unfractionated heparin in diabetic patients undergoing elective PCI. Thirty diabetic patients were randomized to receive during PCI either bivalirudin (bivalirudin group, n=15) or eptifibatide plus heparin (eptifibatide group, n=15) at standard dosing regimens. The drugs were continued for 20 minutes (bivalirudin) or 18 hours (eptifibatide) after PCI. Blood thrombogenicity was assessed using the Badimon ex vivo perfusion chamber. Each patient underwent two perfusion studies - at baseline (on aspirin and clopidogrel) and 15-20 minutes following PCI. Perfusion studies were performed at rheologic conditions of low and high shear rates (LSR, HSR). Porcine aortic tunica media served as the thrombogenic substrate. Aortic specimens were stained for total platelet-thrombus and fibrin deposition. Thrombus area was measured using computerized planimetry. There were no differences in clinical characteristics or baseline thrombus area between the two groups. Total platelet-thrombus area was reduced significantly in both groups, but the degree of reduction was lower in the bivalirudin group compared with the eptifibatide group (HSR: 69.5% vs. 89.3% reduction, respectively, P=0.04; LSR: 50.6% vs. 73.2%, P=0.03). Fibrin deposition was reduced in both groups by 47-49%. In conclusion, both bivalirudin and the combination of eptifibatide plus heparin, given to diabetic patients during PCI, achieved marked reductions in total thrombus formation and fibrin deposition. However, glycoprotein IIb/IIIa inhibition by eptifibatide caused a more pronounced reduction in thrombus formation.

Tolerability and feasibility of eptifibatide in acute coronary syndrome in patients at high risk for cardiovascular disease: A retrospective analysis

Background: Despite the beneficial effects of glycoprotein (GP) IIb/IIIa antagonists in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), GP IIb/IIIa antagonists are rarely administered in general internal medicine wards in Israel, where most patients with UA/ NSTEMI are admitted, due to lack of adequate monitoring and safety concerns. Objective: The aims of this study were to compare the prevalence of bleeding complications in patients with UA/NSTEMI receiving combination treatment with eptifibatide (a GP IIb/IIIa antagonist), the low-molecular-weight heparin enoxaparin, and acetylsalicylic acid (ASA) versus that in patients receiving enoxaparin and ASA in internal medicine wards in Israel, and to identify risk factors for bleeding complications. Methods: This retrospective analysis included information from the database at Rambam Medical Center, Haifa, Israel. The database provided information from 4 of the 5 wards (the ward from which data were unavailable did not routinely use eptifibatide). Data were included from patients aged ≥l.8 years who were admitted to the center with a diagnosis of UA/NSTEMI, were at high risk for death and/or nonfatal ischemic events based on American College of Cardiology/American Heart Association guidelines, were to undergo coronary intervention, and who had a Thrombosis in Myocardial Infarction risk score ≥3 (moderate to high risk). Patients in the eptifibatide group received eptifibatide IV (180-μg/kg bolus followed by a continuous infusion of 2 μg/kg · min up to 72 hours), enoxaparin SC (2 mg/kg · d), and ASA (100 mg/d). Patients in the control group received enoxaparin SC (2 mg/kg - d up to 96 hours) and ASA (100 mg/d). The prevalence of bleeding events was assessed using data up to 24 hours after the end of study drug administration. Major bleeding was defined as life-threatening bleeding at any site, intracranial hemorrhage, or bleeding accompanied by a decrease in plasma hemoglobin concentration of 5 g/dL or more. Otherwise, bleeding was considered minor. The risk for bleeding events was assessed using multivariate regression analysis. Results: Data from 105 patients (64 men, 41 women) were included in the analysis. In the eptifibatide and control groups, the mean (SD) ages were 68.7 (11.1) and 74.8 (11.0) years, respectively. These characteristics were statistically similar between the 2 groups. The rates of major bleeding were similar between the eptifibatide and control groups (2 [3.8%] vs 0 patients). The rate of minor bleeding was significantly higher in the eptifibatide group compared with that in controls (11 [21.2%] vs 4 [7.5%] patients; P = 0.03). The incidence of thrombocytopenia was statistically similar between the eptifibatide and control groups (0 vs 2 [3.8%] patients). The risk for bleeding was found to be associated with eptifibatide use (odds ratio, 4.8; 95% CI, 1.29–17.80), whereas an association with treatment was not found in the control group. Conclusion: The results of this retrospective analysis suggest that the risk for bleeding complications is higher with combination treatment with eptifibatide, enoxaparin, and ASA compared with that with enoxaparin and ASA in high-risk patients with UA/NSTEMI admitted to internal medicine wards in Israel.

Bivalirudin compared with IIb/IIIa inhibitors in patients with in-stent restenosis undergoing intracoronary brachytherapy

Bivalirudin is replacing heparin in percutaneous coronary interventions (PCIs), including vascular brachytherapy (VBT). The aim of the study was to compare bivalirudin with eptifibatide in patients with in-stent restenosis (ISR) undergoing PCI and VBT. One hundred forty-four patients treated with bivalirudin as a single antithrombotic agent were compared with 150 patients treated with eptifibatide. Bivalirudin as a bolus of 0.75 mg/kg followed by 1.75 mg/kg/h infusion until the end of the procedure, and eptifibatide as a double bolus of 180 microg/kg followed by 2 microg/kg/min infusion for 18 h after the procedure were used. The main outcome measures were in-hospital events and 30-day clinical outcomes. Baseline clinical characteristics were similar except that patients in the eptifibatide group were younger (P=.02) and had more saphenous vein graft lesions (P<.001). Patients in the bivalirudin group had a higher number of lesions in the right coronary artery (P<.001) and a higher number of vessels treated (P<.001). Postprocedure creatinine phosphokinase (CPK)-MB levels were significantly lower in the bivalirudin group (P<.03). In-hospital events showed significantly less minor bleeding (P=.01) and a trend toward lower major bleeding and major adverse cardiac events (MACE) in the bivalirudin group (P=.06). Thirty-day outcomes showed a significantly lower incidence of non-Q-wave myocardial infarction (MI) in the bivalirudin group (P=.004). Bivalirudin, as a single antithrombotic agent during PCI and VBT, is associated with significantly lower postprocedural CPK-MB elevation, minor bleeding complications, 30-day non-Q-wave MI rates, and a trend toward lower major bleeding and in-hospital MACE when compared with eptifibatide.

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: An intravital fluorescence microscopy study in pigs

Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.

The impact of adjunctive eptifibatide therapy with percutaneous coronary intervention for acute myocardial infarction

The role of small molecules anti-glycoprotein (GP) IIb/IIIa pharmacotherapy during acute myocardial infarction (AMI) has not been established. The purpose of our study was to evaluate the clinical outcomes of patients sustaining AMI who underwent emergent percutaneous coronary intervention (PCI) and who were distinguished by the use of the anti-GP IIb/IIIa agent eptifibatide. We studied a consecutive group of 216 patients who underwent PCI for acute ST-elevation myocardial infarction and compared the outcomes of patients who received eptifibatide just prior and following the procedure (n=167) to those who were not on anti GP IIb/IIIa inhibitors (n=49). On average, patients treated using eptifibatide were younger and were more likely to be men, hypertensive, and smokers. The eptifibatide treated patients were less likely to have diabetes and renal failure and had worse angiographic characteristics. There were no significant differences between the groups in any of the clinical outcomes, including the composite endpoint (e.g. death, MI, repeat revascularization) and the rate of sub-acute stent thrombosis. Nonetheless, there was a non-significant trend towards lower 30 day mortality in the eptifibatide group (4.8% versus 12%, P=0.09). We concluded that in our comparative study of periprocedural administration of eptifibatide during emergent AMI angioplasty, there was a non-significant trend towards better short-term survival among eptifibatide treated patients although the composite endpoint did not differ between patients distinguished by the use of anti GP IIb/IIIa small molecule pharmacotherapy.

GPIIb–IIIa antagonists reduce thromboinflammatory processes in patients with acute coronary syndromes undergoing percutaneous coronary intervention

To investigate the effects of abciximab, eptifibatide and no GPIIb-IIIa antagonist (control) on soluble CD40 ligand (sCD40L) and the formation of leukocyte-platelet aggregates (LPA) in 98 ACS patients undergoing percutaneous coronary intervention (PCI). sCD40L and LPA are increased in patients with ACS. sCD40L was measured by enzyme-linked immunosorbent assay (ELISA) and LPA by whole blood flow cytometry. There were no baseline differences between the three groups in sCD40L and LPA. At the end of PCI, sCD40L was unchanged in the controls, decreased by 30% (P < 0.001) in the abciximab group and by 11% (P < 0.02) in the eptifibatide group. Eighteen to 24 h after PCI, sCD40L was unchanged in the controls, reduced 30% (P < 0.001) in the abciximab-treated group and 9% (P < 0.01) in the eptifibatide-treated group. At the end of PCI, circulating monocyte-platelet aggregates (MPA) were reduced by 12% (P = NS) in the abciximab-treated group, 13% in the eptifibatide-treated group (P = NS), but slightly increased in the controls (P = NS). Eighteen to 24 h after PCI, MPA were reduced by 41% (P < 0.001) compared to baseline in the abciximab-treated group, by 23% (P = NS) in the eptifibatide-treated group, and 15% (P = NS) in the controls. In contrast to control patients presenting while on clopidogrel, control patients presenting not on clopidogrel demonstrated a reduction in sCD40L and LPA 18-24 h post-PCI (P = NS). At low receptor occupancy, GPIIb-IIIa antagonists did not augment the release of sCD40L or the number of circulating LPA. GPIIb-IIIa antagonists reduce circulating sCD40L and LPA formation in patients with ACS undergoing PCI. At low receptor occupancy, GPIIb-IIIa antagonists do not activate platelets.

Effect of bivalirudin on length of stay in the recovery area after percutaneous coronary intervention compared with heparin alone, heparin + abciximab, or heparin + eptifibatide

Three hundred nine patients were followed during their recovery area stay after percutaneous coronary intervention. Recovery area times for patients who received bivalirudin during percutaneous coronary intervention showed an average reduction in total recovery area length of stay of 36 minutes (p <0.0001) compared with patients who received heparin alone. This reduction was also seen when compared with the heparin + abciximab group (46-minute reduction, p = 0.0007), and the heparin + eptifibatide group (35-minute reduction, p = 0.0005). Patients who received bivalirudin took significantly less time for the activated clotting time (ACT) to normalize despite significantly higher average ACTs and significantly fewer subtherapeutic ACTs.

Prehospital Therapy With the Platelet Glycoprotein IIb/IIIa Inhibitor Eptifibatide in Patients With Suspected Acute Coronary Syndromes: The Bochum Feasibility Study

To assess the practical application and safety of prehospital antithrombotic therapy with the glycoprotein (GP) IIb/IIIa inhibitor eptifibatide for patients with suspected acute coronary syndrome (ACS) or myocardial infarction (MI). Open-labeled pilot study. Patients with typical chest pain who were seen within 6 h of the onset of symptoms were enrolled in the mobile emergency ambulance. Patients were stratified by even/uneven days to receive standard treatment or standard treatment plus an IV bolus of eptifibatide (180 microg/kg body weight) followed by a continuous eptifibatide infusion (2 microg/kg/min). The main outcome measurement was a combination of prehospital or in-hospital death, reinfarction, revascularization of target vessels, and major bleeding complications. A total of 356 patients (age range, 29 to 75 years; women, 24.7%) were included in the analysis. On admission to the hospital, the diagnosis of ACS or MI was confirmed in approximately 60% of patients, and alternative diagnoses were made in 40% of patients. The rates of complications, including fatal and nonfatal complications occurring during transportation and during subsequent hospitalization, were similar in both study groups. The primary end point occurred in 11.8% of patients in the control group, and in 9.6% of those in the eptifibatide group (difference not significant). The prehospital administration of the GP IIb/IIIa inhibitor eptifibatide is feasible and safe in patients with clinically suspected ACS and MI. The benefit of this treatment has yet to be established in a large-scale multicenter study.

Therapeutic use of intravenous eptifibatide in patients undergoing percutaneous coronary intervention: acute coronary syndromes and elective stenting.

Eptifibatide, a molecule isolated from the venom of the southeastern pygmy rattlesnake, selectively inhibits the platelet receptor IIb/IIIa. The safety and clinical efficacy of eptifibatide in patients undergoing percutaneous coronary intervention (PCI) was first evaluated in the Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) trial. In this study, the primary combined endpoint (composite of death, myocardial infarction [MI] or target vessel revascularization [TVR] at 30 days) occurred in 9.6% of the patients assigned to eptifibatide bolus followed by the 4-hour infusion versus 12.2% in the placebo group (p = 0.67). In the IMPACT-II trial, two different eptifibatide dosages were studied in 4011 patients undergoing elective PCI. The primary endpoint (death, MI, TVR or stent placement for threatened vessel closure at 30 days) occurred in 11.6% in the placebo group versus 9.1% in the 135/0.5 eptifibatide group (p = 0.035) and 10% in the 135/0.75 eptifibatide group (p = 0.18). The Enhanced Suppression of Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial studied a dose of eptifibatide 3- to 4-fold higher than that used in IMPACT II trial in patients undergoing non-emergent coronary artery stenting (two 180 microg/kg bolus doses 10 minutes apart). The 6-month composite endpoint (death, MI, TVR and 'bailout' eptifibatide use) occurred in 18.3% of patients in the placebo group versus 14.2% in the eptifibatide group (p = 0.008) and was maintained at 12 months (22.1% in the placebo group vs 17.5% in the eptifibatide group, p = 0.0068). The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) study in 10 948 patients was designed to study the effect of eptifibatide in the treatment of acute coronary syndromes (ACS) using two different dosages (180 microg/kg bolus followed by an infusion of either 1.3 microg/kg/min or 2 microg/kg/min. The primary endpoint, a composite of death or MI at 30 days, occurred in 15.7% of placebo-treated patients and 14.2% of eptifibatide-treated patients (p = 0.042). This difference was maintained at 7 days (11.6% in the placebo group vs 10.1% in the eptifibatide group, p = 0.016) and at 30 days (15.7% in the placebo group vs 14.2% in the eptifibatide group). In the eptifibatide studies, the rates of major bleeding were 0.7% (0.5% in the control group) in ESPRIT and 2.1% (1.3% in the placebo group) in PURSUIT. The incidence of intracranial bleeding was 0.2% in ESPRIT (0.1% in the placebo group) and 0.7% in PURSUIT (0.8% in the placebo group). Significant thrombocytopenia (platelet count <20 000/microL) was reported in 0.2% of the patients receiving eptifibatide in the ESPRIT trial (0% in the placebo group) and in <1% in PURSUIT (<1% in the placebo group). In summary, several clinical trials have demonstrated a clear-cut reduction in a variety of ischemic events in patients receiving eptifibatide as adjunctive pharmacotherapy during PCI.

Evaluating the benefits of glycoprotein IIb/IIIa inhibitors in heart failure at baseline in acute coronary syndromes

BackgroundWe evaluated whether the use of glycoprotein IIb/IIIa receptor inhibitors, in addition to heparin and aspirin, imparts an incremental benefit in a subgroup of patients with acute coronary syndromes (ACS) who had congestive heart failure (CHF) symptoms at presentation. MethodsWe analyzed patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized, double-blind, placebo-controlled study evaluating the use of eptifibatide versus placebo for patients with ACS without persistent ST-elevation. We compared the clinical characteristics and 30-day outcomes for 861 patients who had Killip class II or III CHF symptoms with those of 8558 patients who had no CHF symptoms. ResultsOdds ratios for the primary end point, 30-day death or non-fatal myocardial infarction, in the placebo group versus the eptifibatide group were similar for patients with and without CHF (odds ratio, 1.11; 95% CI, 0.8–1.5; odds ratio, 1.13; 95% CI, 1.0–1.3). However, adverse events were almost twice as frequent for patients with CHF compared with patients with no CHF (24.5% vs 14%). ConclusionsAlthough patients with non-ST–segment elevation ACS who have CHF have markedly worse outcomes than patients without CHF symptoms, we did not find an incremental benefit from the use of eptifibatide in this seriously ill subgroup.

Acute procedural complications and in-hospital events after percutaneous coronary interventions: Eptifibatide versus Abciximab

Background: Glycoprotein IIb/IIIa antagonists reduce peri-angioplasty ischemic complications and improve in-hospital outcome in patients undergoing percutaneous coronary interventions (PCI). Prior studies have demonstrated favorable results with both eptifibatide and abciximab. The purpose of this study was to assess whether there are any differences in rates of acute procedural complications and in-hospital events with the use of these two agents. Methods: A retrospective review of 359 elective PCIs from June 1998 to August 2000 identified 152 PCIs treated with eptifibatide (bolus 180 μg/kg, infusion 2 μg/kg/min for 12–48 h) and 205 PCIs treated with abciximab (bolus 0.25 mg/kg, infusion 10 μg/min for 12 h). All patients received IIb/IIIa antagonists at the initiation of the intervention. Results: The clinical demographics, the angiographic morphology, the indications, and the procedural details were similar in both groups. In the eptifibatide group, the maximum ACT was lower (235±45 vs. 253±40, P<.0001). The incidence of major procedural and in-hospital events was compared. Eptifibatide and abciximab had similar rates of major complications (death or myocardial infarction) (1.4% vs. 2.9%), repeat PTCA (3.4% vs. 1.9%), and major bleeding (3.3% vs. 4.3%). Conclusions: Eptifibatide is comparable to abciximab in regards to acute procedural complications and in-hospital events after PCI.

Comparison of one-year outcomes following coronary artery stenting in diabetic versus nondiabetic patients (from the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy [ESPRIT] Trial)

For patients undergoing nonurgent coronary stent implantation, blockade of the glycoprotein IIb/IIIa receptor with eptifibatide reduces the incidence of ischemic complications. We evaluated the interaction of eptifibatide with diabetes in patients who underwent this procedure by analyzing the 1-year outcomes of those enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial (466 diabetic and 1,595 nondiabetic patients). At 1 year, the composite end point of death, myocardial infarction (MI), or target vessel revascuarlization (TVR) was higher in diabetic patients (24.5% vs 18.4%; p = 0.008). At 1 year, eptifibatide had a similar effect on the composite end point of death, MI, or TVR in diabetic (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.49 to 1.04) and nondiabetic patients (HR 0.80, 95% CI 0.63 to 0.99). A similar treatment effect was also seen on death or MI in both groups. The 1-year mortality rate for diabetic patients assigned to placebo was 3.5% versus 1.3% for patients receiving eptifibatide (HR 0.37, 95% CI 0.10 to 1.41); the latter rate was similar to the mortality rate of 1.4% for nondiabetic patients in the eptifibatide group. However, eptifibatide did not have a significant effect on TVR in diabetic patients (HR 0.90, 95% CI 0.57 to 1.41). Our data suggest that treatment with eptifibatide is associated with a similar relative reduction in adverse ischemic complications in diabetic and nondiabetic patients undergoing coronary stent implantation. There is no evidence of a statistical interaction in the treatment effect of eptifibatide between patients with and without diabetes.

El eptifibatide reduce los valores de proteína C reactiva tras angioplastia coronaria

We measured C-reactive protein concentrations in 31 patients with interventional procedures after blocking thrombosis in 17 of them by the administration of a 12 hour long infusion of eptifibatide in order to evaluate the role of arterial thrombosis. There were no differences in C reactive protein concentration between the treated and control group pre-angioplasty (0.32 0.4 vs 0.56 0.57 md/dl; p = NS), nor post-angioplasty (0.35 0.42 vs 0.53 0.5 mg/dl, p = Ns). The eptifibatide group maintained basal C reactive protein concentrations 6 hours after the procedure, while the control group had a significant increase (0.43 0.5 vs 1.02 0.89 mg/dl; p < 0.05). There was a decrease in C reactive protein 24 hours after angioplasty in eptifibatide group (0.24 0.27 vs 1.34 0.89 mg/dl; p < 0.001), but it increased again 48 hours after the procedure although to a lesser extent than in the control group (0.57 0.55 vs 2.18 2.1 mg/dl; p < 0.05). Eptifibatide, a synthetic peptide which is a selective blocker of the platelet GP IIb/IIIa receptor significantly reduced C-reactive protein concentration after angioplasty.

Comparative 30-day economic and clinical outcomes of platelet glycoprotein IIb/IIIa inhibitor use during elective percutaneous coronary intervention: Prairie ReoPro versus Integrilin Cost Evaluation (PRICE) Trial

Objectives This study examined the economics, pharmacodynamics, and clinical outcomes among patients randomly assigned to receive either abciximab (ReoPro, Centocor, Inc, Malvern, Pa, and Eli Lilly & Company, Indianapolis, Ind) or eptifibatide (Integrilin, COR Therapeutics, Inc, South San Francisco, Calif, and Key Pharmaceuticals, Inc, Kenilworth, NJ) therapy during elective percutaneous coronary intervention (PCI). Background Clinical and safety outcomes after elective PCI with a high-dose eptifibatide treatment strategy have not previously been systematically evaluated. In addition, comparative economic and pharmacodynamic studies of platelet glycoprotein (GP) IIb/IIIa receptor antagonists during PCI are sparse. Methods This randomized, double-blind study assessed the 30-day economic and clinical outcomes of 320 consecutive patients undergoing elective coronary balloon angioplasty or stent implantation who were randomly assigned to receive adjunct abciximab (n = 163) or eptifibatide (n = 157) therapy. The primary study end point was total in-hospital costs based on an intention-to-treat analysis. A secondary end point included 30-day total hospital costs. A platelet aggregometry substudy was performed on 155 patients (abciximab: n = 74 and eptifibatide: n = 81) with use of the Ultegra Rapid Platelet Function Assay. Results Baseline demographic, angiographic, and procedural variables were similar between the two treatment groups. The median and interquartile ranges of total in-hospital costs were $8268 ($6505, $9958) and $7207 ($5659, $9307), respectively, between the abciximab- and eptifibatide-treated patients (P =.009). Median total costs at 30 days were $8336 ($6505, $10,126) and $7207 ($5659, $9431), respectively, between the abciximab- and eptifibatide-treated groups (P =.009). The composite secondary clinical end points (death/nonfatal myocardial infarction/urgent revascularization) occurred in 4.9% versus 5.1% of patients, respectively, by hospital discharge (P =.84) and in 5.6% versus 6.3% of patients, respectively, at 30 days (P =.95) in the abciximab and eptifibatide groups. With the eptifibatide dose used, early and more durable platelet inhibition was achieved compared with abciximab (P <.00001). Conclusion In drug dosages and patients similar to those enrolled in the current study, eptifibatide achieved durable platelet inhibition throughout drug infusion and was associated with lower in-hospital and 30-day costs compared with abciximab in patients undergoing elective PCI. (Am Heart J 2001;141:402-9.)

Evaluación económica de eptifibatide

The aim of this study was to perform an economic evaluation of the PURSUIT trial in Spain, and to measure the cost per year of life saved in patients treated with this drug. PURSUIT is a large, randomised multicentric study on the treatment of unstable angina or non Q wave myocardial infarction with eptifibatide versus placebo, The data on resource consumption provided by the PURSUIT trial were grouped in several populations according to geographical and resource consumption criteria. Unitary costs of these resources were calculated using an "upward" approach that combines individual costs to obtain total costs of several processes and lengths of hospital stay. Cost analysis compares the costs of the initial admission and of the following six months (total cost per patient) for both placebo and eptifibatide. Cost-effectiveness analysis is calculated from total costs and years of life saved calculated according to projections made from results of PURSUIT for Western Europe. The average 6 month cost for the patients who received placebo varies from 0.91 to 1.41 million pesetas, and from 0.96 to 1.45 million pesetas for those treated with eptifibatide. The mean survival was 16.07 years in the placebo group versus 16.11 years in eptifibatide group; 2.9 years of life were saved for every 100 patients treated. The incremental cost of each year of life saved ranges from 1.3 to 3.3 million pesetas. Results vary depending on resource consumption data used. The cost per year of life saved is within the limits considered acceptable for a new technology.