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Alexander G G Turpie - One of the best experts on this subject based on the ideXlab platform.
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Fondaparinux combined with intermittent pneumatic compression vs intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery a randomized double blind comparison
Journal of Thrombosis and Haemostasis, 2007Co-Authors: Alexander G G Turpie, Michael Gent, Joseph A Caprini, Kenneth A Bauer, James E MuntzAbstract:Summary. Background: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. Objectives: To compare the efficacy and safety of Fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. Patients and Methods: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either Fondaparinux 2.5 mg or placebo s.c. for 5–9 days, starting 6–8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. Results: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the Fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9–87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of Fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving Fondaparinux and five (0.8%) receiving placebo had died. Conclusions: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, Fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.
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efficacy and safety of Fondaparinux for the prevention of venous thromboembolism in older acute medical patients randomised placebo controlled trial
BMJ, 2006Co-Authors: Alexander T Cohen, Alexander G G Turpie, Bruce L Davidson, Martin H Prins, A S Gallus, Michael R Lassen, Witold Tomkowski, Jan F M Egberts, Anthonie W A LensingAbstract:Objective To determine the efficacy and safety of the anticoagulant Fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. Design Double blind randomised placebo controlled trial. Setting 35 centres in eight countries. Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. Interventions 2.5 mg Fondaparinux or placebo subcutaneously once daily for six to 14 days. Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. Results 425 patients in the Fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with Fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the Fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the Fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both Fondaparinux and placebo treated patients.
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Fondaparinux in the management of patients with ST-elevation acute myocardial infarction
Vascular health and risk management, 2006Co-Authors: Alexander G G TurpieAbstract:The death rate of patients with ST-segment elevation myocardial infarction (STEMI) remains substantial. Fondaparinux is a synthetic selective Factor Xa inhibitor with a high efficacy and good safety, in terms of bleeding risk, in the prevention and treatment of venous thromboembolism, and in the treatment of non-ST elevation acute coronary syndromes (OASIS-5). The OASIS-6 trial was a randomized, double-blind trial comparing Fondaparinux 2.5 mg once daily with standard therapy, either placebo or unfractionated heparin according to the indication, in 12092 patients with STEMI. At day 30, Fondaparinux significantly reduced the occurrence of the primary efficacy outcome (death or recurrent myocardial infarction) by 14% (p = 0.008). Consistent reductions in both death and recurrent MI were observed at 6-month follow-up. The benefits were significant in patients who received no reperfusion therapy or a thrombolytic agent, but not in patients undergoing primary percutaneous coronary interventions. There was a trend (p = 0.13) towards fewer severe bleeds in the Fondaparinux group (1.0% vs 1.3% in the control group). In conclusion, Fondaparinux significantly reduced mortality without increasing severe bleeding in patients with STEMI. Overall, the data from the OASIS studies showed that Fondaparinux 2.5 mg may represent a new anticoagulant standard in patients with acute coronary syndromes.
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The safety of Fondaparinux for the prevention and treatment of venous thromboembolism.
Expert opinion on drug safety, 2005Co-Authors: Alexander G G TurpieAbstract:Fondaparinux is the first synthetic selective Factor Xa inhibitor. Along with its antithrombotic efficacy, the safety of Fondaparinux has been documented in several Phase II and III clinical trials, including the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery or high-risk abdominal surgery, or in acutely ill medical patients with restricted mobility, and the treatment of patients with deep-vein thrombosis and pulmonary embolism. In all these indications, the safety of Fondaparinux used according to its registered regimen was similar to that of reference comparators. In conclusion, due to its superior efficacy and satisfactory safety, Fondaparinux may substantially improve the prevention and treatment of venous thrombosis.
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superiority of Fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points
Chest, 2004Co-Authors: Alexander G G Turpie, Kenneth A Bauer, Bengt I Eriksson, Michael R LassenAbstract:Study objectives: To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the Fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. Setting and patients: Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. Interventions: Patients were randomized to receive either subcutaneous Fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. Results: Using the original end point of the Fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the Fondaparinux group, with a common odds reduction of 55.2% (p 10 17 ; 95% confidence interval, 45.8% to 63.1%) in favor of Fondaparinux. The respective incidences of efficacy end points with enoxaparin and Fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of Fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. Conclusions: Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used. (CHEST 2004; 126:501–508)
Lars Wallentin - One of the best experts on this subject based on the ideXlab platform.
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association between the use of Fondaparinux vs low molecular weight heparin and clinical outcomes in patients with non st segment elevation myocardial infarction
JAMA, 2015Co-Authors: Karolina Szummer, Jonas Oldgren, Lars Lindhagen, Juan Jesus Carrero, Marie Evans, Jonas Spaak, Robert Edfors, Stefan H Jacobson, Pontus Andell, Lars WallentinAbstract:Importance Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non–ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of Fondaparinux vs LMWH in a nontrial setting is lacking. Objective To study the association between the use of Fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden. Design, Setting, and Patients Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40 616 consecutive patients with NSTEMI who received Fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. Exposures In-hospital treatment with Fondaparinux or LMWH during the hospital stay. Main Outcomes and Measures In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization. Results In total, 14 791 patients (36.4%) were treated with Fondaparinux and 25 825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the Fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the Fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups. Conclusions and Relevance In routine clinical care of patients with NSTEMI, Fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.
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efficacy and safety of Fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention results from the oasis 5 trial
Journal of the American College of Cardiology, 2007Co-Authors: Shamir R Mehta, Ron J.g. Peters, Jean-pierre Bassand, Christopher B Granger, David P Faxon, Rizwan Afzal, John W Eikelboom, Lars Wallentin, Andrzej Budaj, Susan ChrolaviciusAbstract:Objectives This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. Background In the OASIS-5 trial, Fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%. Methods The OASIS-5 trial was a double-blind, randomized comparison of Fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the Fondaparinux group, intravenous Fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was 6 h. Results Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p 6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p Conclusions Upstream therapy with Fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of Fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream Fondaparinux.
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comparison of Fondaparinux and enoxaparin in acute coronary syndromes
The New England Journal of Medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored Fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).
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effects of Fondaparinux on mortality and reinfarction in patients with acute st segment elevation myocardial infarction the oasis 6 randomized trial
JAMA, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:CONTEXT: Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. OBJECTIVE: To evaluate the effect of Fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind comparison of Fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either Fondaparinux or placebo according to the original randomized assignment. MAIN OUTCOME MEASURES: Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). RESULTS: Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the Fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] Fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] Fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of Fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, Fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for Fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with Fondaparinux at 9 days. CONCLUSION: In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, Fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00064428.
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Comparison of Fondaparinux and enoxaparin in acute coronary syndromes.
The New England journal of medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P
Kenneth A Bauer - One of the best experts on this subject based on the ideXlab platform.
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Fondaparinux combined with intermittent pneumatic compression vs intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery a randomized double blind comparison
Journal of Thrombosis and Haemostasis, 2007Co-Authors: Alexander G G Turpie, Michael Gent, Joseph A Caprini, Kenneth A Bauer, James E MuntzAbstract:Summary. Background: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. Objectives: To compare the efficacy and safety of Fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. Patients and Methods: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either Fondaparinux 2.5 mg or placebo s.c. for 5–9 days, starting 6–8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. Results: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the Fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9–87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of Fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving Fondaparinux and five (0.8%) receiving placebo had died. Conclusions: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, Fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.
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superiority of Fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points
Chest, 2004Co-Authors: Alexander G G Turpie, Kenneth A Bauer, Bengt I Eriksson, Michael R LassenAbstract:Study objectives: To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the Fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. Setting and patients: Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. Interventions: Patients were randomized to receive either subcutaneous Fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. Results: Using the original end point of the Fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the Fondaparinux group, with a common odds reduction of 55.2% (p 10 17 ; 95% confidence interval, 45.8% to 63.1%) in favor of Fondaparinux. The respective incidences of efficacy end points with enoxaparin and Fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of Fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. Conclusions: Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used. (CHEST 2004; 126:501–508)
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Fondaparinux, the first selective factor Xa inhibitor.
Current opinion in hematology, 2003Co-Authors: Alexander G G Turpie, Bengt I Eriksson, Michael R Lassen, Kenneth A BauerAbstract:Fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) is a pentasaccharide that selectively inhibits factor Xa; it is the first of a new class of synthetic antithrombotic agents. Fondaparinux has a linear pharmacokinetic profile allowing once-daily subcutaneous administration. Absence of metabolism, complete bioavailability, and lack of nonspecific binding in plasma contribute to the predictability of its effect. Fondaparinux has been approved for use in the prophylaxis of venous thromboembolism following orthopedic surgery. In this setting, it was found to reduce VTE risk by more than 50% in comparison with the low molecular weight heparin enoxaparin, with an incidence of clinically important bleeding not significantly different from that of standard low molecular weight heparin regimens. Furthermore, 4 weeks of prophylaxis with Fondaparinux after hip fracture surgery was shown to reduce the risk of venous thromboembolism by 96% compared with 1-week prophylaxis. Finally, the efficacy and safety of Fondaparinux in the treatment of venous thromboembolism and acute coronary syndromes appears promising.
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Fondaparinux: basic properties and efficacy and safety in venous thromboembolism prophylaxis.
American journal of orthopedics (Belle Mead N.J.), 2002Co-Authors: Kenneth A BauerAbstract:The synthetic pentasaccharide Fondaparinux is the first in a novel class of antithrombotic agents. By selectively inactivating factor Xa in an antithrombin-dependent mechanism of action, Fondaparinux exerts its anticoagulant effect through inhibition of thrombin generation, without any direct effect on thrombin activity. Unlike unfractionated heparin and low-molecular-weight heparins, Fondaparinux is a single molecular entity produced by total chemical synthesis. Its favorable pharmacokinetic profile and pharmacodynamics allow for safe and effective once-daily dosing in the majority of populations. Initial clinical development of Fondaparinux has focused on the prevention of venous thromboembolism following major orthopedic surgery--that is, hip and knee replacement and hip fracture. Results of the largest phase III clinical trial program to date in these major hip and knee surgeries demonstrate comparable safety, in terms of clinically relevant bleeding, and an overall 55% reduction in risk of venous thromboembolism with Fondaparinux relative to the low-molecular-weight heparin enoxaparin.
Ron J.g. Peters - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention results from the oasis 5 trial
Journal of the American College of Cardiology, 2007Co-Authors: Shamir R Mehta, Ron J.g. Peters, Jean-pierre Bassand, Christopher B Granger, David P Faxon, Rizwan Afzal, John W Eikelboom, Lars Wallentin, Andrzej Budaj, Susan ChrolaviciusAbstract:Objectives This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. Background In the OASIS-5 trial, Fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%. Methods The OASIS-5 trial was a double-blind, randomized comparison of Fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the Fondaparinux group, intravenous Fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was 6 h. Results Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p 6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p Conclusions Upstream therapy with Fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of Fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream Fondaparinux.
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comparison of Fondaparinux and enoxaparin in acute coronary syndromes
The New England Journal of Medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored Fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).
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effects of Fondaparinux on mortality and reinfarction in patients with acute st segment elevation myocardial infarction the oasis 6 randomized trial
JAMA, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:CONTEXT: Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. OBJECTIVE: To evaluate the effect of Fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind comparison of Fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either Fondaparinux or placebo according to the original randomized assignment. MAIN OUTCOME MEASURES: Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). RESULTS: Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the Fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] Fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] Fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of Fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, Fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for Fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with Fondaparinux at 9 days. CONCLUSION: In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, Fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00064428.
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Comparison of Fondaparinux and enoxaparin in acute coronary syndromes.
The New England journal of medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P
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randomized blinded trial comparing Fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention arixtra study in percutaneous coronary intervention a randomized evaluation aspire pilot trial
Circulation, 2005Co-Authors: Shamir R Mehta, Ron J.g. Peters, Jean-pierre Bassand, Philippe Gabriel Steg, Christopher B Granger, David P Faxon, Jeffrey I Weitz, Rizwan Afzal, Bonnie Rush, Madhu K NatarajanAbstract:Background— Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of Fondaparinux in the percutaneous coronary intervention (PCI) setting. Methods and Results— A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg Fondaparinux IV, or 5.0 mg Fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined Fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P =0.61). Bleeding was less common in the 2.5-mg Fondaparinux group compared with the 5-mg Fondaparinux group (3.4% versus 9.6%, P =0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the Fondaparinux group, with no significant difference in efficacy among the Fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that Fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 ( P =0.02). Conclusions— In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant Fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of Fondaparinux in arterial thrombosis. Received July 19, 2004; revision received December 13, 2004; accepted December 21, 2004.
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efficacy and safety of Fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention results from the oasis 5 trial
Journal of the American College of Cardiology, 2007Co-Authors: Shamir R Mehta, Ron J.g. Peters, Jean-pierre Bassand, Christopher B Granger, David P Faxon, Rizwan Afzal, John W Eikelboom, Lars Wallentin, Andrzej Budaj, Susan ChrolaviciusAbstract:Objectives This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. Background In the OASIS-5 trial, Fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%. Methods The OASIS-5 trial was a double-blind, randomized comparison of Fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the Fondaparinux group, intravenous Fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was 6 h. Results Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p 6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p Conclusions Upstream therapy with Fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of Fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream Fondaparinux.
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Efficacy and safety of Fondaparinux in patients with acute coronary syndromes
Expert review of cardiovascular therapy, 2007Co-Authors: Jean-pierre Bassand, Isabelle Richard-lordereau, Yves CadroyAbstract:Fondaparinux (Arixtra®, GlaxoSmithKline) is a synthetic, selective, activated Factor X inhibitor. On the grounds of its favorable benefit:risk ratio, Fondaparinux is approved for the prevention and treatment of venous thromboembolism. Two large trials involving approximately 32,000 patients recently evaluated Fondaparinux in the treatment of non-ST elevation acute coronary syndromes and ST elevation acute myocardial infarction. Fondaparinux was compared with enoxaparin or usual care, depending on the setting. A single, once-daily 2.5-mg subcutaneous dose of Fondaparinux was used in both studies. After a brief introduction to the drug, this article presents the results obtained in these trials with Fondaparinux and compares them with those obtained with other anticoagulants. Overall, it appears that Fondaparinux at the single, once-daily dose of 2.5 mg represents a valuable new alternative for the treatment of patients with acute coronary syndromes.
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comparison of Fondaparinux and enoxaparin in acute coronary syndromes
The New England Journal of Medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored Fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).
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effects of Fondaparinux on mortality and reinfarction in patients with acute st segment elevation myocardial infarction the oasis 6 randomized trial
JAMA, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:CONTEXT: Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. OBJECTIVE: To evaluate the effect of Fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind comparison of Fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either Fondaparinux or placebo according to the original randomized assignment. MAIN OUTCOME MEASURES: Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). RESULTS: Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the Fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] Fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] Fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of Fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, Fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for Fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with Fondaparinux at 9 days. CONCLUSION: In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, Fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00064428.
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Comparison of Fondaparinux and enoxaparin in acute coronary syndromes.
The New England journal of medicine, 2006Co-Authors: Salim Yusuf, Ron J.g. Peters, Jean-pierre Bassand, Shamir R Mehta, Christopher B Granger, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Janice Pogue, Lars WallentinAbstract:BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether Fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either Fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with Fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the Fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the Fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with Fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P