Background: In worldwide, the mortality rate of acute myocardial infarction(AMI) raises year by year. Although the applications of percutaneous coronary intervention(PCI) and anticoagulants effectively reduce the mort...Background: In worldwide, the mortality rate of acute myocardial infarction(AMI) raises year by year. Although the applications of percutaneous coronary intervention(PCI) and anticoagulants effectively reduce the mortality of patients with acute coronary syndrome(ACS), but also increase the incidence of bleeding. Therefore, drugs with stable anticoagulant effects are urgently required.Methods: We enrolled 894 patients with acute coronary syndrome who underwent percutaneous coronary intervention in Shenyang Northern Hospital from February 2010 to May 2012; 430 patients were included in the fondaparinux group(2.5mg/d), and 464 were included in the enoxaparin group(1mg/kg twice daily). Fondaparinux and enoxaparin were applied for 3–7 days. All patients were treated with tirofiban [10μg/kg for 3min initially and 0.15μg/(kg·min) for 1 to 3 days thereafter]. The primary efficacy endpoint was the incidence of a major adverse cerebrovascular or cardiovascular event. The primary safety endpoint was bleeding within 30 days and 1 year after percutaneous coronary intervention.Results: One-year data were available for 422 patients in the fondaparinux group and for 453 in the enoxaparin group. The incidence of a major adverse cerebrovascular or cardiovascular event(10.9% vs 12.6%, P=0.433) and cardiac mortality(0.5% vs 1.5%, P=0.116) were generally lower in the fondaparinux group than in the enoxaparin group, although the differences were not significant. Compared with the enoxaparin group, the fondaparinux group had a significantly decreased rate of bleeding at 30 days(0.9% vs 2.9%, P=0.040) and 1 year(2.4% vs 5.5%, P=0.018). In addition, the rate of major bleeding events was lower in the fondaparinux group, but this difference was not significant(0.2% vs 0.9%, 0.2% vs 1.1%).Conclusion: In tirofiban-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention, fondaparinux presented similar efficacy for ischemia events as enoxaparin. However, fondaparinux significantly decreased the incidence of bleeding, thus providing safer anticoagulation therapy.展开更多
In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.T...In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.Though parenteral anticoagulation is essential at the time of diagnosis,a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants.Adverse events associated with anticoagulants,such as heparin-induced thrombocytopenia,bleeding problems,and the need for close monitoring of anticoagulant activity,have contributed to finding agents that reduce these limitations.Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum.The convenience of administration(once daily),lack of monitoring,reduction in mortality,and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.展开更多
Context: Despite many therapeutic advances, mortality in patients with acute S T-segment elevation myocardial infarction(STEMI) remains high. The role of addi tional antithrombotic agents is unclear, especially among ...Context: Despite many therapeutic advances, mortality in patients with acute S T-segment elevation myocardial infarction(STEMI) remains high. The role of addi tional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective: To evaluate the effect of fondaparinux, a facto r Xa inhibitor, when initiated early and given for up to 8 days vs usual care(pl acebo in those in whom unfractionated heparin[UFH] is not indicated[stratum 1] o r 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: Randomiz ed 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(Septe mber 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main O utcome Measures: Composite of death or reinfarction at 30 days(primary) with sec ondary 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 fondaparin ux 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 ob served 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%] fonda parinux; HR, 0.88; 95%CI, 0.79-0.97; P=.008). Mortality was significantly redu ced throughout the study. There was no heterogeneity of the effects of fondapari nux in the 2 strata by planned heparin use. However, there was no benefit in tho se undergoing primary percutaneous coronary intervention. In other patients in s tratum 2, fondaparinux was superior to unfractionated heparin in preventing deat h or reinfarction at 30 days(HR, 0.82; 95%CI, 0.66-1.02; P=.08) and at study e nd(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 a ny 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 car diac tamponade(48 vs 28; P=.02) with fondaparinux at 9 days. Conclusion: In pati ents with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction wit hout increasing bleeding and strokes.展开更多
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 therefor...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.展开更多
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 controlle...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.展开更多
Acute Coronary Syndrome (ACS) is one of the major causes of death worldwide, including unstable angina, ST-segment elevation myocardial infarction and NST-segment elevation myocardial infarction. ACS refers to a serie...Acute Coronary Syndrome (ACS) is one of the major causes of death worldwide, including unstable angina, ST-segment elevation myocardial infarction and NST-segment elevation myocardial infarction. ACS refers to a series of life-threatening heart diseases, which is caused by rupturing coronary plaque and releasing thrombin activation. Then thrombin is activated and generates plaque and thrombosis, which increases the risk of cardiac death and myocardial infarction. Aggressive and conservative treatment is available in clinic practice. Anticoagulant therapy is usually the first choice for conservative treatment and used in combination with dual antiplatelet drugs, which plays an important role in the treatment of acute coronary syndrome. Fondaparinux as a commonly used anticoagulant drug is both antithrombotic effectively and can reduce the risk of bleeding and coronary microvascular dysfunction in the pathogenesis of ischemic heart disease. However, it increased the rate of bleeding. People pay more attention to the role of long-term prognosis. Domestic and foreign researches contrast outcomes of acute coronary syndrome of fondaparinux and low molecular weight heparin.展开更多
Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthe...Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood, Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their α-and β-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity, is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.展开更多
Background American College of Cardiology/American Heart Association/European Society of Cardiology （ACC/AHA/ESC） guidelines gave fondaparinux a class Ⅰ recommendation for use in patients with non-ST elevation acut...Background American College of Cardiology/American Heart Association/European Society of Cardiology （ACC/AHA/ESC） guidelines gave fondaparinux a class Ⅰ recommendation for use in patients with non-ST elevation acute coronary syndromes （NSTE-ACS） undergoing invasive or conservative strategy. Nadroparin is one of the common anticoagulants used in NSTE-ACS in China. Accordingly, this study compared the safety and efficacy between fondaparinux and nadroparin in patients with NSTE-ACS.Methods In this prospective, randomized, open-label, and single center study, a total of 300 patients with NSTE-ACS were randomized to receive either fondaparinux （group F, n=150, 2.5 mg/d） or nadroparin （group N, n=150, 0.1 ml/10 kgq12 h） for a mean of 4 days. The primary safety endpoint was the incidence of major or minor bleeding at 9 days that was not related to coronary artery bypass grafting （CABG）. The primary efficacy endpoints included death, myocardial infarction, or recurrent ischemia at 9 days. All patients underwent a 180-day follow-up.Results Baseline characteristics were well matched between the two groups. There was a non-significant 28% relative risk reduction in the primary safety endpoint in group F compared with group N （4.7% vs. 6.7%, HR 0.72, 95% CI0.42-1.65, P=0.38）. The primary efficacy endpoint was 8.0% in group F and 10.0% in group N （HR, 0.82, 95% CI0.54-1.71, P=0.49）. The composite of the safety and efficacy endpoints at 9 days （10.0% vs. 16.0%, HR 0.61, 95% CI0.31-1.10,P=0.10）, 30 days （14.0% vs. 17.9%, HR 0.72, 95% C/0.47-1.16, P=0.21）, or 180 days （18.7% vs. 27.3%, HR0.65, 95% CI0.38-1.11, P=0.11） showed a non-significant trend toward a lower value in group F.Conclusion Fondaparinux resulted in a nonsignificant risk reduction in patients with NSTE-ACS in both bleeding and ischaemic events during short- and long-term follow-up compared with nadroparin.展开更多
Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with po...Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F （18 patients）, the patients were treated with fondaparinux sodium, 2.5 rag, 1/d for 11 d. In group L （18 patients）, the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome （MODS） and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer. Results： The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L （p 〈 0.05）. Antithrombin Ⅲ got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and llth d （p 〈 0.05）. Fibrinogen levels were gradually increased, and there was no significant difference between two groups （p 〉 0.05）. D-dimer was significantly decreased after anticoagulant therapy for 5 d （p 〈 0.01 ）, and there were significant differences between two groups on the 5th d and 7th d （p 〈 0.05）. It showed no significant difference on the llth d （p 〉 0.05）. Conclusion： Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.展开更多
文摘Background: In worldwide, the mortality rate of acute myocardial infarction(AMI) raises year by year. Although the applications of percutaneous coronary intervention(PCI) and anticoagulants effectively reduce the mortality of patients with acute coronary syndrome(ACS), but also increase the incidence of bleeding. Therefore, drugs with stable anticoagulant effects are urgently required.Methods: We enrolled 894 patients with acute coronary syndrome who underwent percutaneous coronary intervention in Shenyang Northern Hospital from February 2010 to May 2012; 430 patients were included in the fondaparinux group(2.5mg/d), and 464 were included in the enoxaparin group(1mg/kg twice daily). Fondaparinux and enoxaparin were applied for 3–7 days. All patients were treated with tirofiban [10μg/kg for 3min initially and 0.15μg/(kg·min) for 1 to 3 days thereafter]. The primary efficacy endpoint was the incidence of a major adverse cerebrovascular or cardiovascular event. The primary safety endpoint was bleeding within 30 days and 1 year after percutaneous coronary intervention.Results: One-year data were available for 422 patients in the fondaparinux group and for 453 in the enoxaparin group. The incidence of a major adverse cerebrovascular or cardiovascular event(10.9% vs 12.6%, P=0.433) and cardiac mortality(0.5% vs 1.5%, P=0.116) were generally lower in the fondaparinux group than in the enoxaparin group, although the differences were not significant. Compared with the enoxaparin group, the fondaparinux group had a significantly decreased rate of bleeding at 30 days(0.9% vs 2.9%, P=0.040) and 1 year(2.4% vs 5.5%, P=0.018). In addition, the rate of major bleeding events was lower in the fondaparinux group, but this difference was not significant(0.2% vs 0.9%, 0.2% vs 1.1%).Conclusion: In tirofiban-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention, fondaparinux presented similar efficacy for ischemia events as enoxaparin. However, fondaparinux significantly decreased the incidence of bleeding, thus providing safer anticoagulation therapy.
文摘In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.Though parenteral anticoagulation is essential at the time of diagnosis,a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants.Adverse events associated with anticoagulants,such as heparin-induced thrombocytopenia,bleeding problems,and the need for close monitoring of anticoagulant activity,have contributed to finding agents that reduce these limitations.Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum.The convenience of administration(once daily),lack of monitoring,reduction in mortality,and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.
文摘Context: Despite many therapeutic advances, mortality in patients with acute S T-segment elevation myocardial infarction(STEMI) remains high. The role of addi tional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective: To evaluate the effect of fondaparinux, a facto r Xa inhibitor, when initiated early and given for up to 8 days vs usual care(pl acebo in those in whom unfractionated heparin[UFH] is not indicated[stratum 1] o r 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: Randomiz ed 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(Septe mber 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main O utcome Measures: Composite of death or reinfarction at 30 days(primary) with sec ondary 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 fondaparin ux 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 ob served 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%] fonda parinux; HR, 0.88; 95%CI, 0.79-0.97; P=.008). Mortality was significantly redu ced throughout the study. There was no heterogeneity of the effects of fondapari nux in the 2 strata by planned heparin use. However, there was no benefit in tho se undergoing primary percutaneous coronary intervention. In other patients in s tratum 2, fondaparinux was superior to unfractionated heparin in preventing deat h or reinfarction at 30 days(HR, 0.82; 95%CI, 0.66-1.02; P=.08) and at study e nd(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 a ny 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 car diac tamponade(48 vs 28; P=.02) with fondaparinux at 9 days. Conclusion: In pati ents with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction wit hout increasing bleeding and strokes.
文摘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.
文摘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.
文摘Acute Coronary Syndrome (ACS) is one of the major causes of death worldwide, including unstable angina, ST-segment elevation myocardial infarction and NST-segment elevation myocardial infarction. ACS refers to a series of life-threatening heart diseases, which is caused by rupturing coronary plaque and releasing thrombin activation. Then thrombin is activated and generates plaque and thrombosis, which increases the risk of cardiac death and myocardial infarction. Aggressive and conservative treatment is available in clinic practice. Anticoagulant therapy is usually the first choice for conservative treatment and used in combination with dual antiplatelet drugs, which plays an important role in the treatment of acute coronary syndrome. Fondaparinux as a commonly used anticoagulant drug is both antithrombotic effectively and can reduce the risk of bleeding and coronary microvascular dysfunction in the pathogenesis of ischemic heart disease. However, it increased the rate of bleeding. People pay more attention to the role of long-term prognosis. Domestic and foreign researches contrast outcomes of acute coronary syndrome of fondaparinux and low molecular weight heparin.
文摘Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood, Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their α-and β-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity, is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.
文摘Background American College of Cardiology/American Heart Association/European Society of Cardiology （ACC/AHA/ESC） guidelines gave fondaparinux a class Ⅰ recommendation for use in patients with non-ST elevation acute coronary syndromes （NSTE-ACS） undergoing invasive or conservative strategy. Nadroparin is one of the common anticoagulants used in NSTE-ACS in China. Accordingly, this study compared the safety and efficacy between fondaparinux and nadroparin in patients with NSTE-ACS.Methods In this prospective, randomized, open-label, and single center study, a total of 300 patients with NSTE-ACS were randomized to receive either fondaparinux （group F, n=150, 2.5 mg/d） or nadroparin （group N, n=150, 0.1 ml/10 kgq12 h） for a mean of 4 days. The primary safety endpoint was the incidence of major or minor bleeding at 9 days that was not related to coronary artery bypass grafting （CABG）. The primary efficacy endpoints included death, myocardial infarction, or recurrent ischemia at 9 days. All patients underwent a 180-day follow-up.Results Baseline characteristics were well matched between the two groups. There was a non-significant 28% relative risk reduction in the primary safety endpoint in group F compared with group N （4.7% vs. 6.7%, HR 0.72, 95% CI0.42-1.65, P=0.38）. The primary efficacy endpoint was 8.0% in group F and 10.0% in group N （HR, 0.82, 95% CI0.54-1.71, P=0.49）. The composite of the safety and efficacy endpoints at 9 days （10.0% vs. 16.0%, HR 0.61, 95% CI0.31-1.10,P=0.10）, 30 days （14.0% vs. 17.9%, HR 0.72, 95% C/0.47-1.16, P=0.21）, or 180 days （18.7% vs. 27.3%, HR0.65, 95% CI0.38-1.11, P=0.11） showed a non-significant trend toward a lower value in group F.Conclusion Fondaparinux resulted in a nonsignificant risk reduction in patients with NSTE-ACS in both bleeding and ischaemic events during short- and long-term follow-up compared with nadroparin.
文摘Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F （18 patients）, the patients were treated with fondaparinux sodium, 2.5 rag, 1/d for 11 d. In group L （18 patients）, the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome （MODS） and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer. Results： The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L （p 〈 0.05）. Antithrombin Ⅲ got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and llth d （p 〈 0.05）. Fibrinogen levels were gradually increased, and there was no significant difference between two groups （p 〉 0.05）. D-dimer was significantly decreased after anticoagulant therapy for 5 d （p 〈 0.01 ）, and there were significant differences between two groups on the 5th d and 7th d （p 〈 0.05）. It showed no significant difference on the llth d （p 〉 0.05）. Conclusion： Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.
