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Robert M Califf - One of the best experts on this subject based on the ideXlab platform.
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angiographic outcomes with early Eptifibatide therapy in non st segment elevation acute coronary syndrome from the early acs trial
American Journal of Cardiology, 2014Co-Authors: Vijay Kunadian, Robert M Califf, Robert P. Giugliano, Gilles Montalescot, Kristin L Newby, Cafer Zorkun, Jianping Guo, Akshay Bagai, Eugene Braunwald, Frans Van De WerfAbstract:Early administration of glycoprotein IIbIIIa inhibitors results in improved angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade (TMPG) among patients with ST-segment elevation myocardial infarction. Whether the same is true in the setting of non–ST-segment elevation acute coronary syndrome is unknown. The goal of the early glycoprotein IIbIIIa inhibition in non–ST-segment elevation acute coronary syndrome (EARLY ACS) angiographic substudy was to compare angiographic outcomes among patients with non–ST-segment elevation acute coronary syndrome who were administered early routine versus delayed provisional Eptifibatide. Of 9,406 patients in the EARLY ACS trial, 2,066 patients were included in the angiographic substudy (early routine Eptifibatide [n = 1,042] or early placebo [n = 1,024] with delayed provisional Eptifibatide after angiography and before percutaneous coronary intervention [PCI]). The angiographic substudy primary end point was the incidence of TMPG 3 before and after PCI. TMPG 3 before (43.7% vs 44.9%, p = 0.58) and after PCI (52.4% vs 50.1%, p = 0.73) was similar for early routine versus delayed provisional Eptifibatide, respectively. Angiographic procedural complications consisting of a composite of loss of side branch, abrupt vessel closure, distal embolization, and no reflow occurred less frequently in early routine group versus delayed provisional group (9.3% vs 13.6%, respectively, p = 0.01). In the EARLY ACS angiographic substudy, the use of early routine Eptifibatide resulted in fewer angiographic procedural complications. These data provide support for the use of Eptifibatide in the catheterization laboratory during high-risk cases merely to prevent angiographic procedural complications.
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routine early Eptifibatide versus delayed provisional use at percutaneous coronary intervention in high risk non st segment elevation acute coronary syndromes patients an analysis from the early glycoprotein iib iiia inhibition in non st segment elev
American Heart Journal, 2013Co-Authors: Akshay Bagai, Robert P. Giugliano, Paul W. Armstrong, Gilles Montalescot, Michael C Gibson, Pierluigi Tricoci, Frans Van De Werf, Jennifer White, Yuliya Lokhnygina, Robert M CaliffAbstract:Aims In the EARLY ACS trial, routine early Eptifibatide was not superior to delayed provisional use at percutaneous coronary intervention (PCI); however, among PCI-treated patients, numerically fewer ischemic end points occurred in the upstream Eptifibatide group. We sought to further explore this finding using methods for examination of treatment effect in this postrandomization subgroup. Methods and results Of 9,406 patients in the EARLY ACS primary analysis cohort, 9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards regression modeling, with PCI as a time-dependent covariate, to examine the effect of routine early versus delayed provisional Eptifibatide among 5,541 patients undergoing PCI and to explore the interaction between treatment with PCI and randomized treatment strategy. After multivariable adjustment, compared with delayed provisional use, routine early Eptifibatide was associated with lower rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR] 0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74-1.29); PCI × randomized treatment interaction term P = .24. Excluding PCI-related MI, the adjusted HR for 30-day death or MI for routine early Eptifibatide versus delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and 1.01 (95% CI 0.79-1.34) for medical management; PCI × randomized treatment interaction term P = .28. Conclusions Consistent with previous literature, upstream treatment with Eptifibatide was associated with improved outcomes in high-risk non–ST-segment elevation acute coronary syndrome patients treated with PCI; however, a nonsignificant interaction term precludes a definite conclusion.
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Clinical pharmacology of higher dose Eptifibatide in percutaneous coronary intervention (the PRIDE study)
The American journal of cardiology, 2001Co-Authors: James E Tcheng, Neal S. Kleiman, Robert M Califf, A. Michael Lincoff, Ian C Gilchrist, J.conor O’shea, Charles J. Davidson, J. David Talley, Cindy L. Grines, Lisa K. JenningsAbstract:This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose Eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; Eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; Eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or Eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize Eptifibatide dosing.
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Prognostic Importance of Concomitant Heparin With Eptifibatide in Acute Coronary Syndromes
The American journal of cardiology, 2001Co-Authors: John G. Peterson, Robert A. Harrington, Matthew T Roe, Robert M Califf, Eric J. Topol, Shelley K Sapp, A. Michael Lincoff, Jaap W. Deckers, Eugene H. Blackstone, Michael S. LauerAbstract:Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of Eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either Eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of Eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, Eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with Eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with Eptifibatide (adjusted relative risk [RR] for heparin-Eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of Eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of Eptifibatide therapy was largely due to confounding and bias.
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enhanced efficacy of Eptifibatide administration in patients with acute coronary syndrome requiring in hospital coronary artery bypass grafting
Circulation, 2000Co-Authors: Steven P. Marso, Cornelius M. Dyke, Neal S. Kleiman, Deepak L Bhatt, Matthew T Roe, Penny L Houghtaling, Marino Labinaz, Maarten L Simmoons, Robert M Califf, Robert A. HarringtonAbstract:Background —Patients with a recent episode of non–ST-segment elevation acute coronary syndrome before CABG have higher rates of operative morbidity and mortality than patients with stable coronary syndromes. The efficacy of administering Eptifibatide to these patients undergoing in-hospital CABG is unknown. Methods and Results —The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomized 10 948 patients to receive either Eptifibatide or placebo. There were 1558 study participants who underwent in-hospital CABG: 692 received placebo, and 866 received Eptifibatide. The main substudy analysis end point was death or myocardial infarction (MI) rates at the 6-month follow-up. The 30-day death or MI rates were 30.8% and 26.1% for the placebo and Eptifibatide groups, respectively ( P =0.041). The benefit of Eptifibatide administration persisted through 6-months of follow-up (32.7% versus 27.6% for placebo versus Eptifibatide, respectively; P =0.029). There was a greater reduction in the 6-month death or MI rate for patients who received Eptifibatide within 72 hours of CABG (33.6% versus 23.8%; P =0.002) compared with the >72-hour group (31.6% versus 32%; P =1.0). The incidence of major bleeding was 56.6% for placebo-treated patients versus 58.2% for Eptifibatide-treated patients ( P =0.7). Conclusions —Eptifibatide administration in patients undergoing in-hospital CABG with a recent episode of a non–ST-segment elevation acute coronary syndrome results in a significant reduction in death or MI that is evident at 7 days and persists through the 6-month follow-up without a significant increase in perioperative bleeding rates.
George A Stouffer - One of the best experts on this subject based on the ideXlab platform.
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Eptifibatide and 7e3 but not tirofiban inhibit αvβ3 integrin mediated binding of smooth muscle cells to thrombospondin and prothrombin
Circulation, 2001Co-Authors: Manjiri Lele, Mansoor Sajid, Nadeem Wajih, George A StoufferAbstract:Background Our objective was to determine whether abciximab, Eptifibatide, or tirofiban inhibited ligand binding to αvβ3 integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds αIIbβ3 on platelets and αvβ3 on HUVECs with similar affinity, whereas Eptifibatide and tirofiban are thought to be highly specific for αIIbβ3. The conclusion that Eptifibatide does not bind vascular αvβ3 integrins may be premature, however, because recent studies have demonstrated that the affinity of αvβ3 for various ligands, including antagonists, is subject to modulation. Methods and Results Abciximab and 7E3, the anti–β3 integrin monoclonal antibody from which abciximab was derived, bound αvβ3 on HASMCs in a specific and saturable manner and with an affinity similar to binding to αIIbβ3 on platelets. 7E3 and Eptifibatide inhibited αvβ3-mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on αvβ5- or β1-mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of Eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited αvβ3-mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, Eptifibatide inhibited αvβ3-mediated responses to soluble TSP by HASMCs and β3 integrin–expressing HEK cells. Conclusions Eptifibatide and 7E3, but not tirofiban, specifically inhibit αvβ3-mediated binding of human smooth muscle and endothelial cells. Received January 26, 2001; revision received April 6, 2001; accepted April 9, 2001.
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Eptifibatide and 7E3, but Not Tirofiban, Inhibit αvβ3 Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin
Circulation, 2001Co-Authors: Manjiri Lele, Mansoor Sajid, Nadeem Wajih, George A StoufferAbstract:Background Our objective was to determine whether abciximab, Eptifibatide, or tirofiban inhibited ligand binding to αvβ3 integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds αIIbβ3 on platelets and αvβ3 on HUVECs with similar affinity, whereas Eptifibatide and tirofiban are thought to be highly specific for αIIbβ3. The conclusion that Eptifibatide does not bind vascular αvβ3 integrins may be premature, however, because recent studies have demonstrated that the affinity of αvβ3 for various ligands, including antagonists, is subject to modulation. Methods and Results Abciximab and 7E3, the anti–β3 integrin monoclonal antibody from which abciximab was derived, bound αvβ3 on HASMCs in a specific and saturable manner and with an affinity similar to binding to αIIbβ3 on platelets. 7E3 and Eptifibatide inhibited αvβ3-mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on αvβ5- or β1-mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of Eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited αvβ3-mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, Eptifibatide inhibited αvβ3-mediated responses to soluble TSP by HASMCs and β3 integrin–expressing HEK cells. Conclusions Eptifibatide and 7E3, but not tirofiban, specifically inhibit αvβ3-mediated binding of human smooth muscle and endothelial cells. Received January 26, 2001; revision received April 6, 2001; accepted April 9, 2001.
Uwe Zeymer - One of the best experts on this subject based on the ideXlab platform.
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upstream clopidogrel use and the efficacy and safety of early Eptifibatide treatment in patients with acute coronary syndrome an analysis from the early glycoprotein iib iiia inhibition in patients with non st segment elevation acute coronary syndrom
Circulation, 2011Co-Authors: Tracy Y Wang, Uwe Zeymer, Robert A. Harrington, Robert P. Giugliano, Gilles Montalescot, Stefan James, Jennifer A White, Pierluigi Tricoci, Frans Van De Werf, Paul W. ArmstrongAbstract:Background-In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography Eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early Eptifibatide in the setting of concurrent upstream clopidogrel use. Methods and Results-In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early Eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early Eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction P = 0.988). Early Eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (P = 0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early Eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata. Conclusions-Routine early Eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit-risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.
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randomized comparison of Eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute st segment elevation myocardial infarction results of the eva ami trial
Journal of the American College of Cardiology, 2010Co-Authors: Uwe Zeymer, Christoph Bode, Alain Margenet, Michael Haude, J M Lablanche, Hubertus Heuer, R Schroder, Stefan Kropff, Ryad Bourkaib, Norbert BanikAbstract:Objectives The aim of this study was to compare Eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI). Background The glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, Eptifibatide, and abciximab in primary PCI. Methods A total of 427 patients with ST-segment elevation myocardial infarctions Results The incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after Eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after Eptifibatide and abciximab, respectively. Conclusions Eptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751)
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The role of Eptifibatide in patients undergoing percutaneous coronary intervention
Expert opinion on pharmacotherapy, 2007Co-Authors: Uwe ZeymerAbstract: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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A review of clinical trials with Eptifibatide in cardiology.
Cardiovascular drug reviews, 2007Co-Authors: Uwe Zeymer, Harm WienbergenAbstract:Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. Additional antithrombin therapy should be given in connection with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical trials (IMPACT-II and ESPRIT) concomitant administration of Eptifibatide to patients undergoing percutaneous coronary intervention (PCI) reduced thrombotic complications. In the PURSUIT trial, in patients with non-ST-elevation acute coronary syndromes, Eptifibatide, compared to placebo, significantly reduced the primary endpoint of death and nonfatal myocardial infarction at 30 days. In patients with STEMI Eptifibatide has been studied as an adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue reperfusion. Current studies are evaluating Eptifibatide as upstream therapy in high-risk patients with NSTE-ACS, in the EARLY-ACS and in comparison with abciximab in patients with primary PCI in the EVA-AMI trial.
Michael C Gibson - One of the best experts on this subject based on the ideXlab platform.
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routine early Eptifibatide versus delayed provisional use at percutaneous coronary intervention in high risk non st segment elevation acute coronary syndromes patients an analysis from the early glycoprotein iib iiia inhibition in non st segment elev
American Heart Journal, 2013Co-Authors: Akshay Bagai, Robert P. Giugliano, Paul W. Armstrong, Gilles Montalescot, Michael C Gibson, Pierluigi Tricoci, Frans Van De Werf, Jennifer White, Yuliya Lokhnygina, Robert M CaliffAbstract:Aims In the EARLY ACS trial, routine early Eptifibatide was not superior to delayed provisional use at percutaneous coronary intervention (PCI); however, among PCI-treated patients, numerically fewer ischemic end points occurred in the upstream Eptifibatide group. We sought to further explore this finding using methods for examination of treatment effect in this postrandomization subgroup. Methods and results Of 9,406 patients in the EARLY ACS primary analysis cohort, 9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards regression modeling, with PCI as a time-dependent covariate, to examine the effect of routine early versus delayed provisional Eptifibatide among 5,541 patients undergoing PCI and to explore the interaction between treatment with PCI and randomized treatment strategy. After multivariable adjustment, compared with delayed provisional use, routine early Eptifibatide was associated with lower rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR] 0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74-1.29); PCI × randomized treatment interaction term P = .24. Excluding PCI-related MI, the adjusted HR for 30-day death or MI for routine early Eptifibatide versus delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and 1.01 (95% CI 0.79-1.34) for medical management; PCI × randomized treatment interaction term P = .28. Conclusions Consistent with previous literature, upstream treatment with Eptifibatide was associated with improved outcomes in high-risk non–ST-segment elevation acute coronary syndrome patients treated with PCI; however, a nonsignificant interaction term precludes a definite conclusion.
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intracoronary Eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein iib iiia receptor occupancy and platelet function the intracoronary Eptifibatide ice
Circulation, 2010Co-Authors: Albert J. Deibele, James E Tcheng, Lisa K. Jennings, Cathy Neva, Angela D. Earhart, Michael C GibsonAbstract:Background— Eptifibatide reduces major adverse cardiac events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Intracoronary bolus administration of Eptifibatide may result in higher levels of platelet glycoprotein IIb/IIIa receptor occupancy in the local coronary bed, disaggregate thrombus in the epicardial artery and microvasculature, and thereby improve coronary flow. Methods and Results— Patients undergoing PCI for an acute coronary syndrome were randomized to either intracoronary or intravenous bolus administration of Eptifibatide. The primary end point was the local glycoprotein IIb/IIIa receptor occupancy measured in the coronary sinus. There were no angiographic, electrophysiological, or other adverse findings attributable to intracoronary Eptifibatide. Platelet glycoprotein IIb/IIIa receptor occupancy was significantly greater with intracoronary versus intravenous administration: first bolus, 94±9% versus 51±15% (P<0.001); and second bolus, 99±2% vers...
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early initiation of Eptifibatide in the emergency department before primary percutaneous coronary intervention for st segment elevation myocardial infarction results of the time to integrilin therapy in acute myocardial infarction titan timi 34 trial
American Heart Journal, 2006Co-Authors: Ajay J. Kirtane, Sabina A. Murphy, Michael C Gibson, Steve Rohrbeck, Venu Menon, Jeffrey Lins, Samer Kazziha, Ivan C Rokos, Nicolas W ShammasAbstract:Background Early restoration of epicardial flow before primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been associated with improved clinical outcomes. Methods We hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor Eptifibatide in the emergency department (ED) would yield superior epicardial flow and myocardial perfusion before primary PCI compared with initiating Eptifibatide after diagnostic angiography in the cardiac catheterization laboratory (CCL). Three hundred forty-three patients with STEMI were randomized to either early ED Eptifibatide (n = 180) or CCL Eptifibatide (n = 163). Results The primary end point (pre-PCI corrected TIMI frame count) was significantly lower (faster flow) with early Eptifibatide (77.5 ± 32.2 vs 84.3 ± 30.7, P = .049). The incidence of normal pre-PCI TIMI myocardial perfusion was increased among patients treated in the ED versus CCL (24% vs 14%, P = .026). There was no excess of TIMI major or minor bleeding among patients treated in the ED versus CCL (6.9% [12/174] vs 7.8% [11/142], P = NS). Conclusion A strategy of early initiation of Eptifibatide in the ED before primary PCI for STEMI yields superior pre-PCI TIMI frame counts, reflecting epicardial flow, and superior TIMI myocardial perfusion compared with a strategy of initiating Eptifibatide in the CCL without an increase in bleeding risk.
Robert A. Harrington - One of the best experts on this subject based on the ideXlab platform.
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upstream clopidogrel use and the efficacy and safety of early Eptifibatide treatment in patients with acute coronary syndrome an analysis from the early glycoprotein iib iiia inhibition in patients with non st segment elevation acute coronary syndrom
Circulation, 2011Co-Authors: Tracy Y Wang, Uwe Zeymer, Robert A. Harrington, Robert P. Giugliano, Gilles Montalescot, Stefan James, Jennifer A White, Pierluigi Tricoci, Frans Van De Werf, Paul W. ArmstrongAbstract:Background-In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography Eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early Eptifibatide in the setting of concurrent upstream clopidogrel use. Methods and Results-In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early Eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early Eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction P = 0.988). Early Eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (P = 0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early Eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata. Conclusions-Routine early Eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit-risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.
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Pharmacodynamics and pharmacokinetics of Eptifibatide in patients with acute coronary syndromes: prospective analysis from PURSUIT.
Circulation, 2001Co-Authors: Barbara E. Tardiff, Robert A. Harrington, Marino Labinaz, A. Michael Lincoff, Lisa K. Jennings, Daniel D. Gretler, Richard F. Potthoff, David A. Vorchheimer, Paul R. Eisenberg, Diane JosephAbstract:Background Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist Eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of Eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial of ACS. Methods and Results Patients were randomly assigned to an intravenous bolus (180 μg/kg) and 72-hour infusion of Eptifibatide (2.0 μg/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma Eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and d-phenylalanyl-l-prolyl-l-arginine chl...
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Prognostic Importance of Concomitant Heparin With Eptifibatide in Acute Coronary Syndromes
The American journal of cardiology, 2001Co-Authors: John G. Peterson, Robert A. Harrington, Matthew T Roe, Robert M Califf, Eric J. Topol, Shelley K Sapp, A. Michael Lincoff, Jaap W. Deckers, Eugene H. Blackstone, Michael S. LauerAbstract:Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of Eptifibatide, a IIb/IIIa inhibitor, in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin. By trial design, patients were randomized to either Eptifibatide or placebo, whereas use of intravenous heparin was left to the discretion of treating physicians. The effect of Eptifibatide on the 30-day composite end point of death or myocardial infarction was studied in patients who received heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered, Eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving heparin, there was no difference in 30-day event rates with Eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of heparin was developed, however, use of heparin did not affect the reduced risk associated with Eptifibatide (adjusted relative risk [RR] for heparin-Eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of Eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of heparin on the benefits of Eptifibatide therapy was largely due to confounding and bias.
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enhanced efficacy of Eptifibatide administration in patients with acute coronary syndrome requiring in hospital coronary artery bypass grafting
Circulation, 2000Co-Authors: Steven P. Marso, Cornelius M. Dyke, Neal S. Kleiman, Deepak L Bhatt, Matthew T Roe, Penny L Houghtaling, Marino Labinaz, Maarten L Simmoons, Robert M Califf, Robert A. HarringtonAbstract:Background —Patients with a recent episode of non–ST-segment elevation acute coronary syndrome before CABG have higher rates of operative morbidity and mortality than patients with stable coronary syndromes. The efficacy of administering Eptifibatide to these patients undergoing in-hospital CABG is unknown. Methods and Results —The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomized 10 948 patients to receive either Eptifibatide or placebo. There were 1558 study participants who underwent in-hospital CABG: 692 received placebo, and 866 received Eptifibatide. The main substudy analysis end point was death or myocardial infarction (MI) rates at the 6-month follow-up. The 30-day death or MI rates were 30.8% and 26.1% for the placebo and Eptifibatide groups, respectively ( P =0.041). The benefit of Eptifibatide administration persisted through 6-months of follow-up (32.7% versus 27.6% for placebo versus Eptifibatide, respectively; P =0.029). There was a greater reduction in the 6-month death or MI rate for patients who received Eptifibatide within 72 hours of CABG (33.6% versus 23.8%; P =0.002) compared with the >72-hour group (31.6% versus 32%; P =1.0). The incidence of major bleeding was 56.6% for placebo-treated patients versus 58.2% for Eptifibatide-treated patients ( P =0.7). Conclusions —Eptifibatide administration in patients undergoing in-hospital CABG with a recent episode of a non–ST-segment elevation acute coronary syndrome results in a significant reduction in death or MI that is evident at 7 days and persists through the 6-month follow-up without a significant increase in perioperative bleeding rates.
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cost effectiveness of platelet glycoprotein iib iiia inhibition with Eptifibatide in patients with non st elevation acute coronary syndromes
Circulation, 2000Co-Authors: Daniel B Mark, Robert A. Harrington, Robert M Califf, Michael A Lincoff, Charlotte L Nelson, Anastasios A Tsiatis, Hope Buell, Kenneth W Mahaffey, Linda Davidsonray, Eric J. TopolAbstract:Background —In the PURSUIT trial, Eptifibatide significantly reduced the 30-day incidence of death and myocardial infarction relative to placebo in 9461 patients with an acute coronary syndrome (unstable angina or non–Q-wave myocardial infarction). Methods and Results —We conducted a 2-part prospective economic substudy of the 3522 US patients enrolled in PURSUIT: (1) an empirical intention-to-treat comparison of medical costs (hospital plus physician) up to 6 months after hospitalization and (2) a lifetime cost-effectiveness analysis. The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with Eptifibatide therapy. The 2 treatment arms had equivalent resource consumption and medical costs (exclusive of the cost of the Eptifibatide regimen) during the index (enrollment) hospitalization ( P =0.78) and up to 6 months afterward ( P =0.60). The average wholesale price of the Eptifibatide regimen was $1217, but a typical hospital discounted price was $1014. The estimated life expectancy from randomization in the US patients was 15.96 years for Eptifibatide and 15.85 years for placebo, an incremental difference of 0.111. The incremental cost-effectiveness ratio for Eptifibatide therapy in US PURSUIT patients was $16 491 per year of life saved. This result was robust through a wide range of sensitivity analyses. The cost-utility ratio for Eptifibatide (using time trade-off defined utilities) was $19 693 per added quality-adjusted life-year. Conclusions —Based on the results observed in the US PURSUIT patients, the routine addition of Eptifibatide to standard care for non–ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.