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达肝素:其在预防和治疗血栓栓塞性疾病方面的药理特性及临床疗效的最新进展

Dalteparin: an update of its pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic disease.

作者信息

Dunn C J, Jarvis B

机构信息

Adis International Limited, Auckland, New Zealand.

出版信息

Drugs. 2000 Jul;60(1):203-37. doi: 10.2165/00003495-200060010-00010.

Abstract

UNLABELLED

Dalteparin is a low molecular weight heparin (LMWH) with a mean molecular weight of 5000. Compared with unfractionated heparin (UFH), the drug has markedly improved bioavailability and increased plasma elimination half-life, and exerts a greater inhibitory effect on plasma activity of coagulation factor Xa relative to its effects on other coagulation parameters. Dalteparin also has less lipolytic activity than UFH. Dalteparin 2500U once daily subcutaneously is of similar antithrombotic efficacy to UFH 5000IU twice daily, and 2 studies have shown superiority over UFH 2 or 3 times daily of dalteparin 5000U once daily in patients requiring surgical thromboprophylaxis. After total hip arthroplasty, dalteparin was superior to adjusted-dosage warfarin and was of greater thromboprophylactic efficacy when given for 35 than for 7 days. Intravenous or subcutaneous dalteparin is as effective as intravenous UFH when given once or twice daily in the initial management of established deep vein thrombosis (DVT). The drug is also effective in long term home treatment. Dalteparin has been shown to be effective in combination with aspirin in the management of unstable coronary artery disease (CAD), with composite end-point data from 1 study suggesting benefit for up to 3 months. Current data indicate potential of the drug in the management of acute myocardial infarction (MI). Dalteparin is also of similar efficacy to UFH, with a single bolus dose being sufficient in some patients, in the prevention of clotting in haemodialysis and haemofiltration circuits. Pharmacoeconomic data indicate that overall costs relative to UFH from a hospital perspective can be reduced through the use of dalteparin in patients receiving treatment for venous thromboembolism. Dalteparin has also been shown to be cost effective when used for surgical thromboprophylaxis. Overall, rates of haemorrhagic complications in patients receiving dalteparin are low and are similar to those seen with UFH.

CONCLUSIONS

Dalteparin is effective and well tolerated when given subcutaneously once daily in the prophylaxis and treatment of thromboembolic disease. The simplicity of the administration regimens used and the lack of necessity for laboratory monitoring facilitate home or outpatient treatment and appear to translate into cost advantages from a hospital perspective over UFH or warfarin. Dalteparin also maintains the patency of haemodialysis and haemofiltration circuits, with beneficial effects on blood lipid profiles and the potential for prophylaxis with a single bolus injection in some patients. Data are also accumulating to show dalteparin to be an effective and easily administered alternative to UFH in patients with CAD.

摘要

未标注

达肝素是一种平均分子量为5000的低分子量肝素(LMWH)。与普通肝素(UFH)相比,该药生物利用度显著提高,血浆消除半衰期延长,对凝血因子Xa的血浆活性抑制作用相对于其对其他凝血参数的作用更强。达肝素的脂解活性也低于UFH。每日一次皮下注射2500U达肝素的抗血栓疗效与每日两次注射5000IU UFH相似,两项研究表明,在需要手术预防血栓形成的患者中,每日一次注射5000U达肝素优于每日注射2次或3次的UFH。全髋关节置换术后,达肝素优于调整剂量的华法林,给药35天的血栓预防效果优于给药7天。在已确诊的深静脉血栓形成(DVT)的初始治疗中,静脉或皮下注射达肝素每日一次或两次与静脉注射UFH效果相同。该药在长期家庭治疗中也有效。已证明达肝素与阿司匹林联合应用在不稳定冠状动脉疾病(CAD)的治疗中有效,一项研究的综合终点数据表明其益处可持续长达3个月。目前的数据表明该药在急性心肌梗死(MI)的治疗中有潜在作用。在预防血液透析和血液滤过回路中的凝血方面,达肝素与UFH疗效相似,在某些患者中单次推注剂量就足够。药物经济学数据表明,从医院角度来看,在接受静脉血栓栓塞治疗的患者中使用达肝素相对于UFH可降低总体成本。达肝素用于手术血栓预防时也已证明具有成本效益。总体而言,接受达肝素治疗的患者出血并发症发生率较低,与UFH相似。

结论

达肝素每日一次皮下给药在血栓栓塞性疾病的预防和治疗中有效且耐受性良好。所用给药方案简单,无需实验室监测,便于家庭或门诊治疗,从医院角度来看似乎转化为相对于UFH或华法林的成本优势。达肝素还能维持血液透析和血液滤过回路的通畅,对血脂谱有有益影响,在某些患者中有单次推注预防的潜力。越来越多的数据表明达肝素是CAD患者中UFH的有效且易于给药的替代药物。

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