Arixtra^TM

[通用名称 ]　fondaparinuxsodium[结构式 ]　　 [药理作用 ]　本品是通过与抗凝血酶Ⅲ (ATⅢ )结合 ,选择性抑制第十因子 (Xa)而发挥抗血栓活性的。它不使凝血酶失活 ,也不影响血小板的功能 ;推荐剂量下不会影响纤维蛋白活性和出血时间。本品抗Xa的活性随药物浓度的增加而增大 ,给药后 3h达到最大活性。动物实验未见本品有明显的致癌性、致突变和致生育损害。[药代动力学 ]　皮下注射本品可迅速完全被吸收 ,生物利用度接近 10 0 %。本品几乎不经肝脏代谢 ,主要以原药经尿清除 ,单剂量注射后 2h左右达到Cmax0 .34mg·L- 1,每日 1次注射后…     

Efficacy and safety of bivalirudin bridging enoxaparin versus fondaparinux in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: evidence from a single-center study

IntroductionThis study aims to compare the safety and efficacy of bivalirudin bridging enoxaparin versus fondaparinux in patients with acute myocardial infarction (AMI) who were undergoing primary percutaneous coronary intervention (PPCI).MethodsThe study is a prospective, natural, and selective interventional trial based on real-world data for 482 AMI patients.ResultsAt the end of the follow-up, the two groups demonstrated similar major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding rates. After propensity score matching (PSM), the fondaparinux group showed greater advantages in reducing MACCE and bleeding events.ConclusionsThe anticoagulation strategy of bivalirudin bridging fondaparinux seems to be superior to that of bivalirudin bridging enoxaparin in patients with AMI undergoing PPCI.     

Prevention and treatment of venous thromboembolism in the elderly patient

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.     

国产瑞替普酶联合磺达肝癸钠治疗急性ST段抬高性心肌梗死32例临床分析

目的:总结国产瑞替普酶联合磺达肝癸钠治疗急性ST段抬高性心肌梗死(STEMI)的临床疗效和安全性。方法:收集2011-03-2011-10我院年龄≤75岁的STEMI患者32例,给予国产瑞替普酶联合磺达肝癸钠治疗,观察临床效果。结果:90min临床判断血管再通24例(75.0%),5例(15.6%)患者接受介入治疗,全部患者住院期间无严重出血、过敏及死亡事件发生。结论:国产瑞替普酶联合磺达肝癸钠是STEMI患者再灌注治疗用药的理想组合。     

Comparison of safety and efficacy between fondaparinux and nadroparin in non-ST elevation acute coronary syndromes

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 kg q12 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% CI 0.42–1.65, P=0.38). The primary efficacy endpoint was 8.0% in group F and 10.0% in group N (HR, 0.82, 95% CI 0.54–1.71, P=0.49). The composite of the safety and efficacy endpoints at 9 days (10.0% vs. 16.0%, HR 0.61, 95% CI 0.31–1.10, P=0.10), 30 days (14.0% vs. 17.9%, HR 0.72, 95% CI 0.47–1.16, P=0.21), or 180 days (18.7% vs. 27.3%, HR 0.65, 95% CI 0.38–1.11, 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. 

     

Absence of an interaction between the synthetic pentasaccharide fondaparinux and oral warfarin

AIMS: To investigate the pharmacokinetic and pharmacodynamic interaction of the antithrombotic pentasaccharide fondaparinux (Org31540/SR90107A), given subcutaneously, and oral warfarin in healthy subjects. METHODS: This study was performed according to a randomised, three-way cross-over, placebo-controlled, double-blind design in 12 healthy male subjects. The treatment consisted of five subcutaneous (s.c.) injections of fondaparinux (4 mg) or placebo at 24 h intervals. Oral dosing of warfarin or placebo was added to the fourth (15 mg) and fifth (10 mg) s.c. injection. Blood samples for pentasaccharide assay, PT and APTT were drawn before the first s.c. dose of the pentasaccharide and over a 6 day period thereafter. RESULTS: Fondaparinux administered to healthy male volunteers alone or in combination with oral warfarin was well tolerated and no serious adverse events were observed. No differences were found in the AUC (43 vs 44 mg l(-1) h), Cmax (645 vs 678 ng ml(-1)) or elimination half-life (13.8 vs 14.1 h) of fondaparinux between the pentasaccharide-only and the combination treatment. The effect of warfarin on PT (mean maximal increase: 8.2 s.) was not influenced by the presence of the pentasaccharide (mean maximal increase in PT: 9.1 s.). After all treatments a small rise in APTT was seen. No further differences could be detected in the pharmacodynamic parameters following the three treatments. CONCLUSIONS: The coadministration of warfarin did not influence the pharmacokinetics of fondaparinux in healthy subjects. PT can still be used to monitor the effect of oral anticoagulants during the switch from antithrombotic treatment with pentasaccharide to full oral anticoagulant therapy.     

The 'precautionary principle' as a guide for future drug development

During the last decade, the 'precautionary principle' health has gained importance. It is an approach to manage uncertain risks and to prevent any damage to the environment or human. A key element is to take action, even if some cause and effect relationships are not fully established scientifically. Although there are also critics of this principle, it is meanwhile, also increasingly implemented in medicine. An important subject is medicinal products of human or animal origin. Manifold official precaution-guided regulations have been stated to improve their safety, particularly to avoid any infection by viruses and pathogens causing transmissible spongiform encephalopathies. In addition to numerous regulations and decisions, it is generally recommended to substitute animal and human-derived products with adequate alternatives wherever possible. This is a great challenge for research and drug development. One option is recombinant proteins, which however, are not generally free of any risk of contamination. Therefore, the best strategy might be the development of synthetic, specifically acting drugs. The most widely used medicinal product of animal origin at present is heparin. Although there has been no indication of any viral contamination, many other reasons suggest its substitution by alternative antithrombotics. These actually promoted the research on new anticoagulants. With the approval of fondaparinux, the first synthetic, selective factor Xa, a first alternative to the porcine-derived heparin has become available. In addition, other synthetic antithrombotics are currently in clinical development. In principle, it is thus possible that the prophylaxis and therapy of thromboembolic diseases will become completely independent of animal-derived drugs, which would be in line with the precautionary principle.