Martineau P, Tawil N
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Ann Pharmacother. 1998 May;32(5):588-98, 601. doi: 10.1345/aph.16450.
To compare the characteristics and clinical efficacy of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep-vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also discussed.
A MEDLINE search (January 1984-October 1997) was used to identify pertinent French and English literature, including clinical trials and reviews on LMWHs and their use in DVT.
Trials comparing dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As studies were numerous, only randomized trials including more than 50 patients were reviewed. Moreover, all patients studied had a first episode of symptomatic DVT confirmed by objective tests (i.e., venography, duplex ultrasonography, impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed in these trials.
Results pertaining to venographic assessment, recurrent thromboembolism, total mortality, and bleeding complications were extracted from the selected studies.
Compared with UFH, LMWHs have a longer plasma half-life, better subcutaneous bioavailability, more predictable anticoagulant response, and require less intense laboratory monitoring. Most trials demonstrate comparable effects on thrombus extension and incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter total mortality. Although animal trials predict a lower hemorrhagic potential for LMWHs, the incidence of bleeding complications is generally similar to that observed with UFH. Outpatient management of DVT with LMWHs has shown comparable safety and efficacy with inpatient UFH use but a shorter hospital stay.
Because LMWHs are as safe and as effective as UFH, and because of their more convenient method of administration, they can be considered valuable alternatives for the treatment of DVT. Savings generated by less intensive laboratory monitoring and the possibility of early hospital discharge and outpatient therapy may outweight the higher acquisition cost of LMWHs.
比较低分子肝素(LMWHs)与普通肝素(UFH)治疗深静脉血栓形成(DVT)的特点及临床疗效。同时讨论不良反应、给药方法及费用问题。
利用MEDLINE检索(1984年1月至1997年10月)来识别相关的法文和英文文献,包括关于LMWHs及其在DVT中应用的临床试验和综述。
选择比较达肝素、依诺肝素、替扎肝素和那屈肝素与UFH的试验。由于研究数量众多,仅回顾了包括50例以上患者的随机试验。此外,所有研究的患者均经客观检查(即静脉造影、双功超声、阻抗体积描记法)确诊为首次发作的有症状DVT。在这些试验中评估了LMWHs的临床疗效和安全性。
从所选研究中提取与静脉造影评估、复发性血栓栓塞、总死亡率和出血并发症有关的结果。
与UFH相比,LMWHs具有更长的血浆半衰期、更好的皮下生物利用度、更可预测的抗凝反应,且所需的实验室监测强度较低。大多数试验表明,在血栓扩展和复发性血栓栓塞发生率方面有相似的效果。与UFH相比,LMWHs不改变总死亡率。虽然动物试验预测LMWHs的出血可能性较低,但出血并发症的发生率通常与UFH观察到的相似。LMWHs门诊治疗DVT已显示出与住院使用UFH具有相当的安全性和疗效,但住院时间较短。
由于LMWHs与UFH一样安全有效,且给药方法更方便,它们可被视为治疗DVT的有价值的替代药物。减少实验室监测强度以及早期出院和门诊治疗的可能性所节省的费用可能超过LMWHs较高的购置成本。