The Experts below are selected from a list of 6471 Experts worldwide ranked by ideXlab platform
Marc Cohen - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of Enoxaparin compared with unfractionated heparin in high risk patients with non st segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the superior yield of the new strategy of Enoxaparin revascularization and glycoprotein iib iiia inhibitors synergy trial
American Heart Journal, 2006Co-Authors: Harvey D White, Marc Cohen, Neal S Kleiman, Kenneth W Mahaffey, Yuliya Lokhnygina, Karen S Pieper, Karen Chiswell, Robert A Harrington, Derek P Chew, John L PetersenAbstract:Background Enoxaparin reduces ischemic events more effectively than unfractionated heparin (UFH) in patients treated conservatively for non–ST-segment elevation acute coronary syndrome. The SYNERGY trial compared these agents in high-risk patients undergoing early invasive treatment. Enoxaparin was noninferior to UFH for the 30-day primary end point of death/myocardial infarction (MI), but modestly increased bleeding. Methods and Results This article compares the outcomes of the 4687 SYNERGY patients (47%) undergoing percutaneous coronary intervention, who were randomized to receive Enoxaparin or UFH. Antithrombotic therapy was administered prerandomization in 78%. Crossover (usually in the catheterization laboratory) to the alternative antithrombotic occurred in 14.6% of Enoxaparin patients and 2.9% of UFH-treated patients ( P P = .318). The rates of death/MI were similar at 30 days (13.1% with Enoxaparin vs 14.2% with UFH, P = .289). GUSTO severe bleeding occurred with similar frequency in both groups (1.5% vs 1.6%, P = .688). TIMI major bleeding was more common with Enoxaparin (3.7% vs 2.5% with UFH, P = .028). Transfusions were more frequent with Enoxaparin than with UFH (6.8% vs 5.4%, P = .047). TIMI major bleeding increased with crossover from Enoxaparin to UFH (from 3.7% to 7.8%) and from UFH to Enoxaparin (from 2.5% to 8.6%). Statistical adjustment to model reasons for crossover did not affect the overall safety and efficacy outcomes. Conclusions In high-risk patients undergoing early percutaneous coronary intervention for acute coronary syndrome, Enoxaparin avoids the need for monitoring and achieves similar effectiveness to UFH but is associated with more bleeding.
-
Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention
The New England Journal of Medicine, 2006Co-Authors: Gilles Montalescot, Marc Cohen, Harvey D White, Richard L Gallo, Gabriel P Steg, Philip E Aylward, Christoph Bode, Massimo Chiariello, Spencer B King, Robert A HarringtonAbstract:Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non–CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, –2.6; 95% confidence interval [CI], –4.7 to –0.6; P = 0.01), but the higher Enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, –2.0; 95% CI, –4.0 to 0.0; P = 0.051). The incidence of major bleeding was significantly reduced in both Enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received Enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mgper-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). Conclusions In elective PCI, a single intravenous bolus of 0.5 mg of Enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844.)
-
Enoxaparin vs unfractionated heparin in high risk patients with non st segment elevation acute coronary syndromes managed with an intended early invasive strategy primary results of the synergy randomized trial
JAMA, 2004Co-Authors: James J Ferguson, Elliott M Antman, Marc Cohen, Kenneth W Mahaffey, Anatoly Langer, R M Califf, Cindy L Grines, Shaun Goodman, Dean J Kereiakes, Christopher C NesselAbstract:CONTEXT Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES To compare the outcomes of patients treated with Enoxaparin vs unfractionated heparin and to define the role of Enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS Subcutaneous Enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS The primary end point occurred in 14.0% (696/4993) of patients assigned to Enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between Enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with Enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.
-
the safety and efficacy of subcutaneous Enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute st segment elevation myocardial infarction patients ineligible for reperfusion tetami a randomized trial
Journal of the American College of Cardiology, 2003Co-Authors: Marc Cohen, Enrique P Gurfinkel, Harvey D White, Gian Franco Gensini, Frans Maritz, Kurt Huber, Ari Timerman, Maria Krzeminskapakula, Nicolas Danchin, Jose SantopintoAbstract:Abstract Objectives The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI) study were to demonstrate that Enoxaparin was superior to unfractionated heparin (UFH) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infarction (STEMI) who do not receive timely reperfusion. Background An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion. Methods A total of 1,224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002. Patients with STEMI ineligible for reperfusion were randomized to Enoxaparin, Enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent angina; the primary analysis was the comparison of the pooled Enoxaparin and UFH groups. Results The incidence of the primary efficacy end point was 15.7% Enoxaparin versus 17.3% for UFH (odds ratio 0.89 [95% confidence interval {CI} = 0.66 to 1.21]) and 16.6% for tirofiban versus 16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial Infarction (TIMI) major hemorrhage rate was 1.5% for Enoxaparin versus 1.3% for UFH (odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds ratio 1.82 [95% CI 0.67 to 4.95]). Conclusions This study did not show that Enoxaparin significantly reduced the 30-day incidence of death, reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients. However, Enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment. Additional therapy with tirofiban did not appear beneficial.
-
randomized double blind safety study of Enoxaparin versus unfractionated heparin in patients with non st segment elevation acute coronary syndromes treated with tirofiban and aspirin the acute ii study
American Heart Journal, 2002Co-Authors: Marc Cohen, Harvey D White, Pierre Theroux, Steven Borzak, Martin J Frey, W Van Mieghem, Fred Senatore, Joy Lis, Robin Mukherjee, Katherine E HarrisAbstract:Background In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and Enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with Enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding. Objective Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with Enoxaparin plus ASA. Methods Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or Enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days. Results The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the Enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the Enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the Enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively). Conclusions Combination therapy with tirofiban plus Enoxaparin appears safe, relative to therapy with tirofiban plus UFH. (Am Heart J 2002;144:470-7.)
Harvey D White - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of Enoxaparin compared with unfractionated heparin in high risk patients with non st segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the superior yield of the new strategy of Enoxaparin revascularization and glycoprotein iib iiia inhibitors synergy trial
American Heart Journal, 2006Co-Authors: Harvey D White, Marc Cohen, Neal S Kleiman, Kenneth W Mahaffey, Yuliya Lokhnygina, Karen S Pieper, Karen Chiswell, Robert A Harrington, Derek P Chew, John L PetersenAbstract:Background Enoxaparin reduces ischemic events more effectively than unfractionated heparin (UFH) in patients treated conservatively for non–ST-segment elevation acute coronary syndrome. The SYNERGY trial compared these agents in high-risk patients undergoing early invasive treatment. Enoxaparin was noninferior to UFH for the 30-day primary end point of death/myocardial infarction (MI), but modestly increased bleeding. Methods and Results This article compares the outcomes of the 4687 SYNERGY patients (47%) undergoing percutaneous coronary intervention, who were randomized to receive Enoxaparin or UFH. Antithrombotic therapy was administered prerandomization in 78%. Crossover (usually in the catheterization laboratory) to the alternative antithrombotic occurred in 14.6% of Enoxaparin patients and 2.9% of UFH-treated patients ( P P = .318). The rates of death/MI were similar at 30 days (13.1% with Enoxaparin vs 14.2% with UFH, P = .289). GUSTO severe bleeding occurred with similar frequency in both groups (1.5% vs 1.6%, P = .688). TIMI major bleeding was more common with Enoxaparin (3.7% vs 2.5% with UFH, P = .028). Transfusions were more frequent with Enoxaparin than with UFH (6.8% vs 5.4%, P = .047). TIMI major bleeding increased with crossover from Enoxaparin to UFH (from 3.7% to 7.8%) and from UFH to Enoxaparin (from 2.5% to 8.6%). Statistical adjustment to model reasons for crossover did not affect the overall safety and efficacy outcomes. Conclusions In high-risk patients undergoing early percutaneous coronary intervention for acute coronary syndrome, Enoxaparin avoids the need for monitoring and achieves similar effectiveness to UFH but is associated with more bleeding.
-
Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention
The New England Journal of Medicine, 2006Co-Authors: Gilles Montalescot, Marc Cohen, Harvey D White, Richard L Gallo, Gabriel P Steg, Philip E Aylward, Christoph Bode, Massimo Chiariello, Spencer B King, Robert A HarringtonAbstract:Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non–CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, –2.6; 95% confidence interval [CI], –4.7 to –0.6; P = 0.01), but the higher Enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, –2.0; 95% CI, –4.0 to 0.0; P = 0.051). The incidence of major bleeding was significantly reduced in both Enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received Enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mgper-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). Conclusions In elective PCI, a single intravenous bolus of 0.5 mg of Enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844.)
-
safety and efficacy of Enoxaparin vs unfractionated heparin in patients with non st segment elevation acute coronary syndromes who receive tirofiban and aspirin a randomized controlled trial
JAMA, 2004Co-Authors: Michael A Blazing, Harvey D White, James A De Lemos, Keith A A Fox, Freek W A Verheugt, Diego Ardissino, Peter M Dibattiste, Joanne Palmisano, David W Bilheimer, Steven M SnapinnAbstract:ContextEnoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non–ST-elevation acute coronary syndromes (ACS). It is not clear if combining Enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors.ObjectiveTo assess efficacy and safety of the combination of Enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non–ST-elevation ACS.Design, Setting, and ParticipantsA prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of Enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non–ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002.Main Outcome MeasuresDeath, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system.ResultsA total of 169 (8.4%) of 2018 patients randomized to Enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored Enoxaparin except death, which occurred in only 1% of patients (23 for Enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for Enoxaparin and 2.2% for unfractionated heparin; P = .13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of Enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated.ConclusionsIn patients receiving tirofiban and aspirin, Enoxaparin is a suitable alternative to unfractionated heparin for treatment of non–ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of Enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.
-
the safety and efficacy of subcutaneous Enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute st segment elevation myocardial infarction patients ineligible for reperfusion tetami a randomized trial
Journal of the American College of Cardiology, 2003Co-Authors: Marc Cohen, Enrique P Gurfinkel, Harvey D White, Gian Franco Gensini, Frans Maritz, Kurt Huber, Ari Timerman, Maria Krzeminskapakula, Nicolas Danchin, Jose SantopintoAbstract:Abstract Objectives The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI) study were to demonstrate that Enoxaparin was superior to unfractionated heparin (UFH) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infarction (STEMI) who do not receive timely reperfusion. Background An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion. Methods A total of 1,224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002. Patients with STEMI ineligible for reperfusion were randomized to Enoxaparin, Enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent angina; the primary analysis was the comparison of the pooled Enoxaparin and UFH groups. Results The incidence of the primary efficacy end point was 15.7% Enoxaparin versus 17.3% for UFH (odds ratio 0.89 [95% confidence interval {CI} = 0.66 to 1.21]) and 16.6% for tirofiban versus 16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial Infarction (TIMI) major hemorrhage rate was 1.5% for Enoxaparin versus 1.3% for UFH (odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds ratio 1.82 [95% CI 0.67 to 4.95]). Conclusions This study did not show that Enoxaparin significantly reduced the 30-day incidence of death, reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients. However, Enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment. Additional therapy with tirofiban did not appear beneficial.
-
randomized double blind safety study of Enoxaparin versus unfractionated heparin in patients with non st segment elevation acute coronary syndromes treated with tirofiban and aspirin the acute ii study
American Heart Journal, 2002Co-Authors: Marc Cohen, Harvey D White, Pierre Theroux, Steven Borzak, Martin J Frey, W Van Mieghem, Fred Senatore, Joy Lis, Robin Mukherjee, Katherine E HarrisAbstract:Background In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and Enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with Enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding. Objective Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with Enoxaparin plus ASA. Methods Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or Enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days. Results The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the Enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the Enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the Enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively). Conclusions Combination therapy with tirofiban plus Enoxaparin appears safe, relative to therapy with tirofiban plus UFH. (Am Heart J 2002;144:470-7.)
Elliott M Antman - One of the best experts on this subject based on the ideXlab platform.
-
Enoxaparin versus unfractionated heparin with fibrinolysis for st elevation myocardial infarction
The New England Journal of Medicine, 2006Co-Authors: Elliott M Antman, Carolyn H Mccabe, Sema Guneri, Mikhail Ruda, Andrzej Budaj, Jose Lopezsendon, Sabina A Murphy, David A Morrow, Zygmunt Sadowski, Frank JiangAbstract:Background Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, Enoxaparin, with unfractionated heparin for this purpose. Methods We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive Enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. Results The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the Enoxaparin group (17 percent reduction in relative risk, P<0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving Enoxaparin (33 percent reduction in relative risk, P<0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given Enoxaparin (P = 0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given Enoxaparin (P<0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given Enoxaparin (P<0.001). Conclusions In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with Enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. (ClinicalTrials.gov number, NCT00077792.)
-
Enoxaparin vs unfractionated heparin in high risk patients with non st segment elevation acute coronary syndromes managed with an intended early invasive strategy primary results of the synergy randomized trial
JAMA, 2004Co-Authors: James J Ferguson, Elliott M Antman, Marc Cohen, Kenneth W Mahaffey, Anatoly Langer, R M Califf, Cindy L Grines, Shaun Goodman, Dean J Kereiakes, Christopher C NesselAbstract:CONTEXT Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES To compare the outcomes of patients treated with Enoxaparin vs unfractionated heparin and to define the role of Enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS Subcutaneous Enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS The primary end point occurred in 14.0% (696/4993) of patients assigned to Enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between Enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with Enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.
-
population pharmacokinetics and pharmacodynamics of Enoxaparin in unstable angina and non st segment elevation myocardial infarction
British Journal of Clinical Pharmacology, 2003Co-Authors: Rene Bruno, Pascale Baille, Sylvie Retout, Nicole Vivier, Christine Veyratfollet, Gerjan Sanderink, Richard C Becker, Elliott M AntmanAbstract:Aims A major concern with any antithrombotic therapy is an increase in the risk of haemorrhage. The aim of this study was to analyse population pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) relationships for Enoxaparin in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI), which may help predict risk of haemorrhage. Methods Anti-factor Xa (anti-Xa) activity was measured as marker of Enoxaparin concentration in 448 patients receiving the drug as a single 30-mg intravenous bolus followed by 1.0 or 1.25 mg kg−1 subcutaneously twice a day. A population pharmacokinetic analysis was conducted and individual estimates of Enoxaparin clearance and area under the curve were tested as prognostic factors for the occurrence of haemorrhagic episodes. Results Basic population PK parameters were an Enoxaparin clearance of 0.733 l h−1[95% confidence interval (CI) 0.698, 0.738], a distribution volume of 5.24 l (95% CI 4.20, 6.28) and an elimination half-life of 5.0 h. Enoxaparin clearance was significantly related to patient weight and creatinine clearance, and was the only independent predictor of experiencing both all (10.7%, P = 0.0013) and major (2.2%, P = 0.0004) haemorrhagic events. A creatinine clearance of 30 ml min−1 was associated with a decrease in Enoxaparin clearance of 27% compared with that in a patient with a median creatinine clearance of 88 ml min−1, and was related to a 1.5- and 3.8-fold increase in the risk of ‘all’ and ‘major’ haemorrhagic episodes, respectively. Conclusions Enoxaparin clearance depends on body weight, and, therefore, weight-adjusted dosing is recommended to minimize interpatient variability in drug exposure and the risk of haemorrhage. The importance of an increased risk of haemorrhage with decreasing renal function must be weighed against the benefit of treatment with Enoxaparin in patients with UA and NSTEMI.
-
Enoxaparin as adjunctive antithrombin therapy for st elevation myocardial infarction results of the entire thrombolysis in myocardial infarction timi 23 trial
Circulation, 2002Co-Authors: Elliott M Antman, Frederique Bigonzi, Hans W Louwerenburg, Hubert F Baars, Jan Wesdorp, Bas Hamer, Jeanpierre Bassand, Ghislaine Pisapia, Michael C Gibson, Hein HeidbuchelAbstract:Background— ENTIRE-TIMI 23 evaluated Enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab. Methods and Results— Patients (n=483) with ST-elevation MI presenting <6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or Enoxaparin (1.0 mg/kg subcutaneously every 12 hours±initial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or Enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hours±initial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with Enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with Enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among Enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4....
Frederique Bigonzi - One of the best experts on this subject based on the ideXlab platform.
-
improved reperfusion and clinical outcome with Enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction the ami sk study
European Heart Journal, 2002Co-Authors: Maarten L Simoons, Shaun G Goodman, M Krzeminskapakula, A Alonso, A Kali, U Loos, F Gosset, V Louer, Frederique BigonziAbstract:Aims To establish whether the addition of Enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction. Methods and Results A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30mg) and subcutaneous injections (1mg.kg−1, twice daily) of Enoxaparin (n=253), or placebo (n=243) for 3–8 days. The median duration of treatment in both groups was 5 days. ST-segment resolution at 90min and 180min measured by electrocardiogram was improved in patients receiving Enoxaparin. Complete, partial and no ST-segment resolution at 180min was observed in 36%, 44% and 19% in the Enoxaparin group vs 25%, 44% and 31% in the placebo group, respectively ( P =0·004). Assessment of the primary end-point revealed improved TIMI-3 flow with Enoxaparin vs placebo (70% vs 58%, P =0·01). Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P =0·001), as was TIMI frame count ( P =0·003). The triple clinical end-point of death, reinfarction and recurrent angina at 30 days was reduced with Enoxaparin (13% vs 21%, P =0·03). Conclusion Streptokinase in combination with Enoxaparin is associated with better ST-segment resolution and better angiographic patency at days 5–10, suggesting more effective reperfusion. This was associated with a significant reduction in clinical events, indicating less reocclusion. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .
-
Enoxaparin as adjunctive antithrombin therapy for st elevation myocardial infarction results of the entire thrombolysis in myocardial infarction timi 23 trial
Circulation, 2002Co-Authors: Elliott M Antman, Frederique Bigonzi, Hans W Louwerenburg, Hubert F Baars, Jan Wesdorp, Bas Hamer, Jeanpierre Bassand, Ghislaine Pisapia, Michael C Gibson, Hein HeidbuchelAbstract:Background— ENTIRE-TIMI 23 evaluated Enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab. Methods and Results— Patients (n=483) with ST-elevation MI presenting <6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or Enoxaparin (1.0 mg/kg subcutaneously every 12 hours±initial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or Enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hours±initial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with Enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with Enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among Enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4....
-
prospective comparison of hemorrhagic complications after treatment with Enoxaparin versus unfractionated heparin for unstable angina pectoris or non st segment elevation acute myocardial infarction
American Journal of Cardiology, 2001Co-Authors: Scott D Berkowitz, Sandra S Stinnett, Marc Cohen, Gregg J Fromell, Frederique BigonziAbstract:Patients with unstable angina pectoris (UAP) or non–ST-segment elevation acute myocardial infarction (AMI) are at risk of death or recurrent ischemic events, despite receiving aspirin and unfractionated heparin (UFH). This study investigates the effect of the low molecular weight heparin, Enoxaparin, on the incidence of hemorrhage and thrombocytopenia in relation to baseline characteristics and subsequent invasive procedures. Rates of hemorrhage and thrombocytopenia were analyzed for UAP or non–ST-segment elevation AMI in patients included in the prospective, randomized, double-blind Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events (ESSENCE) study. Patients received either Enoxaparin or UFH, plus aspirin, for 2 to 8 days. The overall rate of major hemorrhage (at 30 days) was comparable between the 2 groups (6.5% for Enoxaparin vs 7.0% for UFH, p = 0.6). The rate of major hemorrhage while on treatment was slightly higher in the Enoxaparin group, but this was not significant (1.1% vs 0.7% for UFH, p = 0.204), as was the rate of major hemorrhage within 48 hours of coronary artery bypass grafting performed within 12 hours of treatment. However, the rate of minor hemorrhage was significantly higher in the Enoxaparin group, with the majority being injection-site ecchymoses or hematomas (11.9% vs 7.2% with UFH, p <0.001). Thrombocytopenia (platelet count <100,000 per mm3) occurred mainly in association with coronary bypass surgery, with a similar rate in both groups. Thus, Enoxaparin is a well-tolerated alternative to UFH in the management of UAP or non–ST-segment elevation AMI. Despite the more effective antithrombotic effect, which results in fewer ischemic events, Enoxaparin is not associated with an increase in the rate of major hemorrhagic complications, and is not significantly associated with thrombocytopenia, but is associated with an increase in minor injection site ecchymosis.
Shintaro Tachibana - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of edoxaban versus Enoxaparin for the prevention of venous thromboembolism following total hip arthroplasty stars j v
Thrombosis Journal, 2015Co-Authors: Takeshi Fuji, Tetsuya Kimura, Masayuki Fukuzawa, Kenji Abe, Satoru Fujita, Yohko Kawai, Mashio Nakamura, Shintaro TachibanaAbstract:In the absence of thromboprophylaxis, patients undergoing total hip arthroplasty (THA) are at increased risk for venous thromboembolism (VTE). The objective of this study was to compare the efficacy and safety of edoxaban with Enoxaparin for the prevention of VTE after THA in Japan. This was a phase 3, double-blind, double-dummy, noninferiority study. Patients undergoing elective, unilateral primary THA were randomized to receive edoxaban 30 mg once daily (n = 307) or Enoxaparin 2000 IU (equivalent to 20 mg) twice daily (n = 303) for 11 to 14 days. The primary efficacy endpoint was the incidence of VTE. Safety endpoints included the incidence of major or clinically relevant nonmajor (CRNM) bleeding. The incidence of VTE, based on venography and clinical surveillance, was 2.4 % in the edoxaban group and 6.9 % in the Enoxaparin group (P <0.001). The absolute difference in the incidence of VTE was −4.5 % (95 % confidence interval [CI]: −8.6, −0.9), which was within the noninferiority margin set at 8 % for the difference and established the noninferiority of edoxaban to Enoxaparin. Since the upper limit of the 95 % CI of the absolute difference was less than 0 %, the superiority of edoxaban over Enoxaparin was demonstrated. The incidence of major or CRNM bleeding was 2.6 % in the edoxaban group and 3.7 % in the Enoxaparin group (P = 0.475). Oral edoxaban 30 mg once daily was superior to subcutaneous Enoxaparin 2000 IU twice daily in the prevention of VTE following THA without increasing the risk for major or CRNM bleeding.
-
safety and efficacy of edoxaban an oral factor xa inhibitor versus Enoxaparin for thromboprophylaxis after total knee arthroplasty the stars e 3 trial
Thrombosis Research, 2014Co-Authors: Takeshi Fuji, Tetsuya Kimura, Kenji Abe, Satoru Fujita, Yohko Kawai, Chingjen Wang, Mashio Nakamura, Kei Ibusuki, Hitoshi Ushida, Shintaro TachibanaAbstract:Abstract Introduction This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with Enoxaparin sodium (Enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan. Materials and methods In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30mg once daily beginning 6 to 24hours postsurgery or Enoxaparin 2000IU (equivalent to 20mg) subcutaneously twice daily beginning 24 to 36hours postsurgery for 11 to 14days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions. Results Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or Enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and Enoxaparin groups, respectively (relative risk reduction=46.8%), indicating non-inferiority ( P P =0.010) of edoxaban versus Enoxaparin. In the edoxaban and Enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients ( P =0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients ( P =0.129), respectively. Conclusions Edoxaban 30mg once daily was more effective for thromboprophylaxis than subcutaneous Enoxaparin 2000IU twice daily following TKA and demonstrated a similar incidence of bleeding events.
-
safety and efficacy of edoxaban an oral factor xa inhibitor versus Enoxaparin for thromboprophylaxis after total knee arthroplasty the stars e 3 trial
Thrombosis Research, 2014Co-Authors: Takeshi Fuji, Tetsuya Kimura, Kenji Abe, Satoru Fujita, Yohko Kawai, Chingjen Wang, Mashio Nakamura, Kei Ibusuki, Hitoshi Ushida, Shintaro TachibanaAbstract:Abstract Introduction This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with Enoxaparin sodium (Enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan. Materials and methods In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or Enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions. Results Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or Enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and Enoxaparin groups, respectively (relative risk reduction = 46.8%), indicating non-inferiority (P Conclusions Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous Enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.
-
Safety and efficacy of edoxaban in patients undergoing hip fracture surgery
Thrombosis research, 2014Co-Authors: Takeshi Fuji, Tetsuya Kimura, Kenji Abe, Satoru Fujita, Yohko Kawai, Mashio Nakamura, Yuichi Kiuchi, Shintaro TachibanaAbstract:Abstract Introduction Edoxaban is an oral, direct, once-daily factor Xa inhibitor. This study evaluated the safety and efficacy of edoxaban compared to subcutaneous Enoxaparin in Japanese patients undergoing hip fracture surgery. Materials and methods In this multicenter, randomized, open-label, active-comparator, phase 3 trial, 92 patients were randomized 2:1 to receive edoxaban 30 mg once daily (n = 62) or Enoxaparin sodium (Enoxaparin) 2000 IU (equivalent to 20 mg) twice daily (n = 30) for 11 to 14 days. The primary endpoints were the incidence of major or clinically relevant non-major (CRNM) bleeding and incidence of any bleeding events (major, CRNM, or minor bleeding). Secondary efficacy endpoints included the incidence of thromboembolic events, venous thromboembolism-related deaths, and all-cause deaths. Additional adverse events were recorded throughout the study. Results In the edoxaban and Enoxaparin treatment groups, the incidence of major or CRNM bleeding was 3.4% and 6.9%, respectively, while any bleeding event occurred in 25.4% and 17.2% of patients, respectively. The incidence of thromboembolic events was 6.5% in the edoxaban group and 3.7% in the Enoxaparin group. All events were asymptomatic deep vein thrombosis. The incidence of adverse events was 72.9% and 82.8% in the edoxaban and Enoxaparin groups, respectively. Conclusions Compared to subcutaneous Enoxaparin 2000 IU twice daily, oral edoxaban 30 mg once daily demonstrated similar safety and efficacy in the prevention of thromboembolic events in Japanese patients undergoing hip fracture surgery. Clinical trials registration number: NCT01181141.