Antman E M
Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Mass 02115, USA.
Am Heart J. 1998 Jun;135(6 Pt 3 Su):S353-60. doi: 10.1016/s0002-8703(98)70265-0.
Continuous intravenous (i.v.) heparin administered in the acute period after unstable coronary artery disease reduces the likelihood and severity of subsequent ischemic events. However, reactivation of the thrombotic process may occur when heparin therapy is withdrawn. Low-molecular-weight heparin provides more reliable anticoagulation and less need for patient monitoring and dosage adjustment than standard unfractionated heparin (UFH) and therefore is well suited for long-term anticoagulation on an outpatient basis. TIMI 11B is a randomized, double-blind, placebo-controlled clinical trial designed to compare the strategy of combined short-term and long-term administration of the low-molecular-weight heparin enoxaparin for unstable angina/non-Q-wave myocardial infarction versus the standard strategy of UFH administration only during the acute phase. Patients are randomized to receive either enoxaparin (30 mg i.v. bolus followed by subcutaneous (s.c.) injections of 1.0 mg/kg every 12 hours) or UFH (70 U/kg bolus followed by an infusion of 15 U/kg per hour, titrated to an activated partial thromboplastin time of 1.5 to 2.5 times control). Infusion of i.v. UFH or placebo continues for a minimum of 72 hours. S.c. weight-adjusted enoxaparin or placebo continues until hospital discharge or day 8, whichever comes first, at which time the long-term phase of the study begins. Patients randomized to receive enoxaparin in the acute phase receive fixed-dose s.c. enoxaparin (60 mg every 12 hours for patients > or =65 kg, 40 mg every 12 hours for patients <65 kg). Patients randomized to receive UFH in the acute phase receive s.c. placebo injections during the chronic phase. The primary efficacy endpoint is the sum, through day 43, of the occurrence of death, nonfatal myocardial infarction not present at enrollment, or severe recurrent ischemia requiring urgent revascularization. The primary safety endpoint is the occurrence of either major bleeding or other serious adverse events.
在不稳定型冠状动脉疾病急性期持续静脉注射肝素可降低后续缺血事件的发生可能性及严重程度。然而，停用肝素治疗时可能会发生血栓形成过程的重新激活。与标准普通肝素（UFH）相比，低分子量肝素提供更可靠的抗凝作用，且对患者监测和剂量调整的需求更少，因此非常适合门诊长期抗凝治疗。TIMI 11B是一项随机、双盲、安慰剂对照的临床试验，旨在比较低分子量肝素依诺肝素短期和长期联合给药策略用于不稳定型心绞痛/非Q波心肌梗死与仅在急性期给予UFH的标准策略。患者被随机分配接受依诺肝素（静脉推注30 mg，随后每12小时皮下注射1.0 mg/kg）或UFH（静脉推注70 U/kg，随后每小时输注15 U/kg，根据活化部分凝血活酶时间调整至对照值的1.5至2.5倍）。静脉注射UFH或安慰剂持续至少72小时。皮下注射根据体重调整剂量的依诺肝素或安慰剂持续至出院或第8天，以先到者为准，此时研究的长期阶段开始。急性期随机接受依诺肝素治疗的患者接受固定剂量皮下注射依诺肝素（体重≥65 kg的患者每12小时60 mg，体重<65 kg的患者每12小时40 mg）。急性期随机接受UFH治疗的患者在慢性期接受皮下注射安慰剂。主要疗效终点是至第43天死亡、入选时不存在的非致命性心肌梗死或需要紧急血运重建的严重复发性缺血的发生总和。主要安全终点是发生大出血或其他严重不良事件。
