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Robert A. Harrington - One of the best experts on this subject based on the ideXlab platform.
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comparison of st segment resolution with combined fibrinolytic and glycoprotein iib iiia inhibitor therapy versus fibrinolytic alone data from four clinical trials
American Journal of Cardiology, 2005Co-Authors: Abdallah G Rebeiz, Robert A. Harrington, Kristin L Newby, Per Johanson, Cynthia L Green, Suzanne W Crater, Anatoly Langer, Robert P Giugliano, Michael A Lincoff, Eric J. TopolAbstract:We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus Lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
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Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials).
The American journal of cardiology, 2005Co-Authors: Abdallah G Rebeiz, Matthew T. Roe, L. Kristin Newby, Per Johanson, Cynthia L Green, Suzanne W Crater, Anatoly Langer, Robert P Giugliano, A. Michael Lincoff, Robert A. HarringtonAbstract:We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus Lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
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An Automated Strategy for Bedside aPTT Determination and Unfractionated Heparin Infusion Adjustment in Acute Coronary Syndromes: Insights from PARAGON A
Journal of Thrombosis and Thrombolysis, 2002Co-Authors: L. Kristin Newby, Eric J. Topol, Robert A. Harrington, Frans Van De Werf, Christopher B. Granger, Manjushri V. Bhapkar, Judith S. Hochman, R. John Simes, Catherine G. Davis, Robert M. CaliffAbstract:Background: Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes. Methods and Results: We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested Lamifiban with or without unfractionated heparin versus unfractionated heparin. All patients had baseline and 6-hour blinded, bedside aPTTs, then aPTTs per algorithm. A central computer translated encrypted values to algorithmic dose-adjustment commands. We assessed the ability to achieve and maintain aPTTs of 50–70 seconds and associations of 6- and 12-hour aPTTs and time-to-target with 30-day outcomes. Overall, the median 6-hour aPTT was 50–70 seconds and remained so throughout infusion. Individually, only 33.6% of patients achieved 6-hour target-range aPTTs, and only 40% of all aPTTs were in-range. After achieving target, only 42% of subsequent measures were in-range. Thirty-day death or myocardial infarction (death/MI) increased non-significantly as time-to-target increased ( p = 0.08). Thirty-day mortality was similar if target aPTT was reached, regardless of timing. Death/MI trended lower if target aPTT was reached by 8 hours ( p = 0.10). The best clinical outcomes were associated with in-range aPTTs. Conclusions: This study represents the most systematic monitoring and regulation of unfractionated heparin anticoagulation to date. Although average anticoagulation achieved target range, wide inter- and intra-patient variability may have important implications for clinical outcomes. Abbreviated abstract: Using systematic aPTT testing and computer-directed, algorithmic unfractionated heparin infusion adjustment in 1,275 acute coronary syndrome patients, the overall median aPTT was 50–70 seconds. However, only 33.6% of patients achieved this target 6-hour aPTT range. Only 40% of all aPTTs, and after achieving target, only 42% of subsequent measures, were in this range. Thirty-day death or myocardial infarction increased with increasing time to target aPTT (for trend, p = 0.08). The best outcomes were associated with 6- and 12-hour aPTTs in the target range. Wide inter- and intra-patient variability despite highly systematic, controlled unfractionated heparin infusion regulation has important implications for unfractionated heparin use.
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Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).
American heart journal, 2002Co-Authors: Debabrata Mukherjee, Robert A. Harrington, David J. Moliterno, Kenneth W. Mahaffey, Jay S. Yadav, Karen S. Pieper, Dianne Gallup, Christopher K. Dyke, Matthew T. Roe, Lisa G. BerdanAbstract:Abstract Background Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors. Methods In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor Lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B. Results Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the Lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the Lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the Lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57−0.79, P P =.465), death/MI at 30 days ( P =.264), and stroke at 30 days with the type of heparin use ( P =.201) after propensity risk adjustment. Conclusions In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome. (Am Heart J 2002;144:995-1002.)
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benefit of glycoprotein iib iiia inhibition in patients with acute coronary syndromes and troponin t positive status the paragon b troponin t substudy
Circulation, 2001Co-Authors: Kristin L Newby, Robert A. Harrington, David J. Moliterno, Magnus E Ohman, Robert H Christenson, Harvey D White, Paul W Armstrong, Frans Van De Werf, Matthias Pfisterer, Vic HasselbladAbstract:Background—Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results—We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive Lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0...
Eric J. Topol - One of the best experts on this subject based on the ideXlab platform.
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comparison of st segment resolution with combined fibrinolytic and glycoprotein iib iiia inhibitor therapy versus fibrinolytic alone data from four clinical trials
American Journal of Cardiology, 2005Co-Authors: Abdallah G Rebeiz, Robert A. Harrington, Kristin L Newby, Per Johanson, Cynthia L Green, Suzanne W Crater, Anatoly Langer, Robert P Giugliano, Michael A Lincoff, Eric J. TopolAbstract:We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus Lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
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An Automated Strategy for Bedside aPTT Determination and Unfractionated Heparin Infusion Adjustment in Acute Coronary Syndromes: Insights from PARAGON A
Journal of Thrombosis and Thrombolysis, 2002Co-Authors: L. Kristin Newby, Eric J. Topol, Robert A. Harrington, Frans Van De Werf, Christopher B. Granger, Manjushri V. Bhapkar, Judith S. Hochman, R. John Simes, Catherine G. Davis, Robert M. CaliffAbstract:Background: Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes. Methods and Results: We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested Lamifiban with or without unfractionated heparin versus unfractionated heparin. All patients had baseline and 6-hour blinded, bedside aPTTs, then aPTTs per algorithm. A central computer translated encrypted values to algorithmic dose-adjustment commands. We assessed the ability to achieve and maintain aPTTs of 50–70 seconds and associations of 6- and 12-hour aPTTs and time-to-target with 30-day outcomes. Overall, the median 6-hour aPTT was 50–70 seconds and remained so throughout infusion. Individually, only 33.6% of patients achieved 6-hour target-range aPTTs, and only 40% of all aPTTs were in-range. After achieving target, only 42% of subsequent measures were in-range. Thirty-day death or myocardial infarction (death/MI) increased non-significantly as time-to-target increased ( p = 0.08). Thirty-day mortality was similar if target aPTT was reached, regardless of timing. Death/MI trended lower if target aPTT was reached by 8 hours ( p = 0.10). The best clinical outcomes were associated with in-range aPTTs. Conclusions: This study represents the most systematic monitoring and regulation of unfractionated heparin anticoagulation to date. Although average anticoagulation achieved target range, wide inter- and intra-patient variability may have important implications for clinical outcomes. Abbreviated abstract: Using systematic aPTT testing and computer-directed, algorithmic unfractionated heparin infusion adjustment in 1,275 acute coronary syndrome patients, the overall median aPTT was 50–70 seconds. However, only 33.6% of patients achieved this target 6-hour aPTT range. Only 40% of all aPTTs, and after achieving target, only 42% of subsequent measures, were in this range. Thirty-day death or myocardial infarction increased with increasing time to target aPTT (for trend, p = 0.08). The best outcomes were associated with 6- and 12-hour aPTTs in the target range. Wide inter- and intra-patient variability despite highly systematic, controlled unfractionated heparin infusion regulation has important implications for unfractionated heparin use.
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platelet glycoprotein iib iiia receptor blockade in coronary artery disease
Journal of the American College of Cardiology, 2000Co-Authors: Michael A Lincoff, Robert M. Califf, Eric J. TopolAbstract:New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and Lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents. During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.
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Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease
Journal of the American College of Cardiology, 2000Co-Authors: A. Michael Lincoff, Robert M. Califf, Eric J. TopolAbstract:New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and Lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents. During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.
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Role of Platelets in Restenosis After Percutaneous Coronary Revascularization
Journal of the American College of Cardiology, 1996Co-Authors: Hervé Le Breton, Edward F. Plow, Eric J. TopolAbstract:The role of platelets in the process of restenosis after percutaneous coronary intervention is not fully understood. After vascular injury there is extensive platelet activation, adhesion, aggregation and secretion. Through the liberation of growth factors, such as platelet-derived growth factor, and surface expression of cell adhesion molecules, such as the glycoprotein IIb/IIIa integrin, platelets appear to be a pivotal mediator of the vascular injury response. Experimental models have demonstrated that profound, prolonged thrombocytopenia, or blockade of the IIb/IIIa receptor, may reduce neointimal hyperplasia after arterial balloon injury. However, multiple clinical trials testing conventional or new platelet agents have not yielded any salutary effects. The recent finding that abciximab, a monoclonal antibody fragment directed against IIb/IIIa, reduced clinical restenosis after coronary angioplasty by 26% in patients raises questions about the mechanism of benefit. The alpha v beta 3 vitronectin receptor is responsible for binding endothelial cells to platelets, and it also has a key role in modulating smooth muscle cell migration. It is possible that the antibody fragment exerts its effect on restenosis by means of alpha v beta 3, because abciximab fully cross-reacts to this integrin owing to the shared beta 3 subunit. To date, the other platelet glycoprotein IIb/IIIa inhibitors, including Integrelin, Tirofiban, Lamifiban and Xemilofiban, are specific in binding to this particular integrin. Considerable further study is necessary to unravel the effects of platelets on the restenosis process.
David J. Moliterno - One of the best experts on this subject based on the ideXlab platform.
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upstream use of small molecule glycoprotein iib iiia inhibitors in patients with non st segment elevation acute coronary syndromes a systematic overview of randomized clinical trials
Circulation-cardiovascular Quality and Outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Kristin L Newby, Harvey D White, Vic Hasselblad, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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Upstream Use of Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes A Systematic Overview of Randomized Clinical Trials
Circulation. Cardiovascular quality and outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Harvey D White, Vic Hasselblad, L. Kristin Newby, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).
American heart journal, 2002Co-Authors: Debabrata Mukherjee, Robert A. Harrington, David J. Moliterno, Kenneth W. Mahaffey, Jay S. Yadav, Karen S. Pieper, Dianne Gallup, Christopher K. Dyke, Matthew T. Roe, Lisa G. BerdanAbstract:Abstract Background Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors. Methods In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor Lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B. Results Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the Lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the Lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the Lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57−0.79, P P =.465), death/MI at 30 days ( P =.264), and stroke at 30 days with the type of heparin use ( P =.201) after propensity risk adjustment. Conclusions In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome. (Am Heart J 2002;144:995-1002.)
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benefit of glycoprotein iib iiia inhibition in patients with acute coronary syndromes and troponin t positive status the paragon b troponin t substudy
Circulation, 2001Co-Authors: Kristin L Newby, Robert A. Harrington, David J. Moliterno, Magnus E Ohman, Robert H Christenson, Harvey D White, Paul W Armstrong, Frans Van De Werf, Matthias Pfisterer, Vic HasselbladAbstract:Background—Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results—We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive Lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0...
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Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy.
Circulation, 2001Co-Authors: L. Kristin Newby, Robert A. Harrington, David J. Moliterno, Robert H Christenson, Harvey D White, Paul W Armstrong, Frans Van De Werf, Matthias Pfisterer, E. Magnus Ohman, Vic HasselbladAbstract:Background—Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results—We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive Lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0...
Frans Van De Werf - One of the best experts on this subject based on the ideXlab platform.
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upstream use of small molecule glycoprotein iib iiia inhibitors in patients with non st segment elevation acute coronary syndromes a systematic overview of randomized clinical trials
Circulation-cardiovascular Quality and Outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Kristin L Newby, Harvey D White, Vic Hasselblad, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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Upstream Use of Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes A Systematic Overview of Randomized Clinical Trials
Circulation. Cardiovascular quality and outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Harvey D White, Vic Hasselblad, L. Kristin Newby, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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An Automated Strategy for Bedside aPTT Determination and Unfractionated Heparin Infusion Adjustment in Acute Coronary Syndromes: Insights from PARAGON A
Journal of Thrombosis and Thrombolysis, 2002Co-Authors: L. Kristin Newby, Eric J. Topol, Robert A. Harrington, Frans Van De Werf, Christopher B. Granger, Manjushri V. Bhapkar, Judith S. Hochman, R. John Simes, Catherine G. Davis, Robert M. CaliffAbstract:Background: Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes. Methods and Results: We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested Lamifiban with or without unfractionated heparin versus unfractionated heparin. All patients had baseline and 6-hour blinded, bedside aPTTs, then aPTTs per algorithm. A central computer translated encrypted values to algorithmic dose-adjustment commands. We assessed the ability to achieve and maintain aPTTs of 50–70 seconds and associations of 6- and 12-hour aPTTs and time-to-target with 30-day outcomes. Overall, the median 6-hour aPTT was 50–70 seconds and remained so throughout infusion. Individually, only 33.6% of patients achieved 6-hour target-range aPTTs, and only 40% of all aPTTs were in-range. After achieving target, only 42% of subsequent measures were in-range. Thirty-day death or myocardial infarction (death/MI) increased non-significantly as time-to-target increased ( p = 0.08). Thirty-day mortality was similar if target aPTT was reached, regardless of timing. Death/MI trended lower if target aPTT was reached by 8 hours ( p = 0.10). The best clinical outcomes were associated with in-range aPTTs. Conclusions: This study represents the most systematic monitoring and regulation of unfractionated heparin anticoagulation to date. Although average anticoagulation achieved target range, wide inter- and intra-patient variability may have important implications for clinical outcomes. Abbreviated abstract: Using systematic aPTT testing and computer-directed, algorithmic unfractionated heparin infusion adjustment in 1,275 acute coronary syndrome patients, the overall median aPTT was 50–70 seconds. However, only 33.6% of patients achieved this target 6-hour aPTT range. Only 40% of all aPTTs, and after achieving target, only 42% of subsequent measures, were in this range. Thirty-day death or myocardial infarction increased with increasing time to target aPTT (for trend, p = 0.08). The best outcomes were associated with 6- and 12-hour aPTTs in the target range. Wide inter- and intra-patient variability despite highly systematic, controlled unfractionated heparin infusion regulation has important implications for unfractionated heparin use.
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benefit of glycoprotein iib iiia inhibition in patients with acute coronary syndromes and troponin t positive status the paragon b troponin t substudy
Circulation, 2001Co-Authors: Kristin L Newby, Robert A. Harrington, David J. Moliterno, Magnus E Ohman, Robert H Christenson, Harvey D White, Paul W Armstrong, Frans Van De Werf, Matthias Pfisterer, Vic HasselbladAbstract:Background—Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results—We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive Lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0...
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Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy.
Circulation, 2001Co-Authors: L. Kristin Newby, Robert A. Harrington, David J. Moliterno, Robert H Christenson, Harvey D White, Paul W Armstrong, Frans Van De Werf, Matthias Pfisterer, E. Magnus Ohman, Vic HasselbladAbstract:Background—Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results—We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive Lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0...
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upstream use of small molecule glycoprotein iib iiia inhibitors in patients with non st segment elevation acute coronary syndromes a systematic overview of randomized clinical trials
Circulation-cardiovascular Quality and Outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Kristin L Newby, Harvey D White, Vic Hasselblad, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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Upstream Use of Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes A Systematic Overview of Randomized Clinical Trials
Circulation. Cardiovascular quality and outcomes, 2011Co-Authors: Pierluigi Tricoci, David J. Moliterno, Harvey D White, Vic Hasselblad, L. Kristin Newby, Robert P Giugliano, David F Kong, Pierre Theroux, Gregg W Stone, Frans Van De WerfAbstract:Background—The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results—Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and Lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated ...
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comparison of st segment resolution with combined fibrinolytic and glycoprotein iib iiia inhibitor therapy versus fibrinolytic alone data from four clinical trials
American Journal of Cardiology, 2005Co-Authors: Abdallah G Rebeiz, Robert A. Harrington, Kristin L Newby, Per Johanson, Cynthia L Green, Suzanne W Crater, Anatoly Langer, Robert P Giugliano, Michael A Lincoff, Eric J. TopolAbstract:We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus Lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
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Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials).
The American journal of cardiology, 2005Co-Authors: Abdallah G Rebeiz, Matthew T. Roe, L. Kristin Newby, Per Johanson, Cynthia L Green, Suzanne W Crater, Anatoly Langer, Robert P Giugliano, A. Michael Lincoff, Robert A. HarringtonAbstract:We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus Lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.
