Van't Hof Arnoud W J, Ten Berg Jurriën, Heestermans Ton, Dill Thorsten, Funck Reinhard C, van Werkum Wouter, Dambrink Jan-Henk E, Suryapranata Harry, van Houwelingen Gert, Ottervanger Jan Paul, Stella Pieter, Giannitsis Evangelos, Hamm Christian
Isala Klinieken, Department of Cardiology, Zwolle, Netherlands.
Lancet. 2008 Aug 16;372(9638):537-46. doi: 10.1016/S0140-6736(08)61235-0.
The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre.
We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297.
936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36).
Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.
在急性ST段抬高型心肌梗死（STEMI）患者中，抗血小板治疗的最佳剂量和时机至关重要。我们研究了在救护车或转诊中心首次医疗接触时早期给予糖蛋白IIb/IIIa抑制剂替罗非班是否能改善直接冠状动脉介入治疗（PCI）的效果。
我们在荷兰、德国和比利时的24个中心进行了一项双盲、随机、安慰剂对照试验。在2006年6月29日至2007年11月13日期间，984例拟行PCI的STEMI患者除接受阿司匹林（500 mg）、肝素（5000 IU）和氯吡格雷（600 mg）治疗外，被随机分配至高剂量推注替罗非班组（n = 491）或安慰剂组（n = 493）。随机分组采用装有研究药物的盲法密封试剂盒，每组4例。主要终点是PCI术后1小时残余ST段偏移程度。分析采用意向性治疗。该试验已注册，注册号为ISRCTN06195297。
936例（95%）患者在救护车中进行院前心肌梗死诊断后被随机分配接受治疗。症状出现至诊断的中位时间为76分钟（四分位间距35 - 150）。高剂量推注替罗非班预处理的患者PCI术前平均残余ST段偏移（10.9 mm [标准差9.2] 对比12.1 mm [9.4]，p = 0.028）和PCI术后1小时（3.6 mm [4.6] 对比4.8 mm [6.3]，p = 0.003）显著低于安慰剂组。两组大出血发生率无显著差异（19例 [4%] 对比14例 [3%]；p = 0.36）。
我们的研究发现，院前常规启动高剂量推注替罗非班可改善PCI术后ST段回落及临床结局，这强调了在接受PCI的STEMI患者中，除大剂量氯吡格雷外，还需进一步抑制血小板聚集。
