普通肝素与比伐卢定在经皮冠状动脉介入治疗（HEAT-PPCI）中的应用：一项开放标签、单中心、随机对照试验。

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

机构信息

Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.

出版信息

Lancet. 2014 Nov 22;384(9957):1849-1858. doi: 10.1016/S0140-6736(14)60924-7. Epub 2014 Jul 4.

DOI:10.1016/S0140-6736(14)60924-7

PMID:25002178

Abstract

BACKGROUND

Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure.

METHODS

In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518.

FINDINGS

Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59).

INTERPRETATION

Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially.

FUNDING

Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

摘要

背景

在直接经皮冠状动脉介入治疗（PPCI）中，比伐卢定联合糖蛋白（GP）IIb/IIIa 抑制剂的选择性应用是公认的标准治疗方法。我们旨在比较在该治疗过程中使用比伐卢定或普通肝素的抗血栓治疗。

方法

在我们的开放性、随机对照试验中，我们连续纳入了在利物浦心脏和胸部医院（英国利物浦）接受 PPCI 治疗的成年患者，这些患者的策略是延迟同意。在血管造影前，我们按照年龄（<75 岁与≥75 岁）和心源性休克（有或无）将患者（1:1；分层）随机分配至肝素（70 U/kg）或比伐卢定（首剂 0.75 mg/kg；输注 1.75 mg/kg/小时）。患者随访 28 天。主要疗效终点是全因死亡率、脑血管意外、再梗死或计划外靶病变血运重建的复合终点。主要安全性终点是大出血发生率（根据 Bleeding Academic Research Consortium 定义为 3-5 级）。本研究在 ClinicalTrials.gov 注册，编号为 NCT01519518。

发现

在 2012 年 2 月 7 日至 2013 年 11 月 20 日期间，我们中心进行紧急血管造影的 1917 例患者中的 1829 例（占试验初治患者的 97%）被随机分配至治疗组，其中 1812 例患者纳入最终分析。在比伐卢定组的 905 例患者中，有 751 例（83%）和肝素组的 907 例患者中有 740 例（82%）接受了经皮冠状动脉介入治疗。两组中 GP IIb/IIIa 抑制剂的使用率大致相同（比伐卢定组 122 例[13%]和肝素组 140 例[15%]）。在比伐卢定组的 905 例患者中，有 79 例（8.7%）和肝素组的 907 例患者中 52 例（5.7%）发生了主要疗效终点事件（绝对风险差异 3.0%；相对风险 [RR] 1.52，95%CI 1.09-2.13，p=0.01）。在比伐卢定组的 905 例患者中，有 32 例（3.5%）和肝素组的 907 例患者中 28 例（3.1%）发生了主要安全性终点事件（0.4%；1.15，0.70-1.89，p=0.59）。