Montalescot G, Collet J P, Lison L, Choussat R, Ankri A, Vicaut E, Perlemuter K, Philippe F, Drobinski G, Thomas D
Department of Cardiology, Pitié-Salpétrière Hospital, Paris.
J Am Coll Cardiol. 2000 Jul;36(1):110-4. doi: 10.1016/s0735-1097(00)00695-1.
We tested the hypothesis that different anticoagulant treatments may produce different platelet effects and von Willebrand factor (vWf) release in unstable angina.
The early increase of vWf has been reported to be a risk factor for adverse outcome in unstable angina. Anticoagulant drugs play a key role in stabilization of unstable angina, but they may not have the same efficacy and the same effects on acute vWf release.
We studied 154 patients enrolled in several clinical trials testing four different anticoagulant treatments in unstable angina or non-Q-wave myocardial infarction. Patients were treated during at least 48 h by either intravenous unfractionated heparin, one of two different low molecular weight heparins (enoxaparin or dalteparin) or the direct thrombin inhibitor PEG-hirudin. All patients received aspirin but no Ib/IIIa inhibitors.
The release of vWf over the first 48 h (delta vWf) did not relate to the baseline clinical characteristics. At 30 days of follow-up, delta vWf was sevenfold higher in patients with an end point (death, myocardial infarction, revascularization) than in patients free of events (+53 +/-7% vs. +7 +/-14%, p = 0.004). The same trend was present for each component of the composite end point with the highest levels for one-month mortality (+87 +/- 32% vs. +26 +/- 8%, p = 0.09). The vWf values did not increase over 48 h in patients receiving either enoxaparin or PEG-hirudin (+10 +/- 9% and -5 +/- 20%, respectively). A serious rise ofvWf was measured in unfractionated heparin-treated patients (+87 +/- 11%), which differed significantly from the enoxaparin group (p = 0.0006) and PEG-hirudin group (p < 0.0001). In dalteparin-treated patients, delta vWf was elevated (+48 +/- 8%) and did not differ from the unfractionated heparin group (NS).
We confirm that, in unstable angina patients, a rise of vWf over the first 48 h is associated with an impaired outcome at 30 days. Moreover, the four different anticoagulant treatments tested here do not provide the same protection with regards to vWf release, which may have important prognostic implications and explain different results observed in recent clinical trials.
我们检验了不同抗凝治疗可能在不稳定型心绞痛中产生不同血小板效应及血管性血友病因子（vWf）释放的假说。
据报道，vWf的早期升高是不稳定型心绞痛不良预后的一个危险因素。抗凝药物在不稳定型心绞痛的病情稳定中起关键作用，但它们对急性vWf释放可能没有相同的疗效和相同的作用。
我们研究了154例参加多项临床试验的患者，这些试验测试了在不稳定型心绞痛或非Q波心肌梗死中四种不同的抗凝治疗。患者接受至少48小时的静脉普通肝素、两种不同低分子肝素（依诺肝素或达肝素）之一或直接凝血酶抑制剂聚乙二醇水蛭素治疗。所有患者均接受阿司匹林治疗，但未使用糖蛋白IIb/IIIa抑制剂。
最初48小时内vWf的释放（ΔvWf）与基线临床特征无关。在随访30天时，发生终点事件（死亡、心肌梗死、血运重建）的患者的ΔvWf比无事件患者高7倍（+53±7%对+7±14%，p = 0.004）。复合终点的每个组成部分都有相同的趋势，1个月死亡率的水平最高（+87±32%对+26±8%，p = 0.09）。接受依诺肝素或聚乙二醇水蛭素治疗的患者在48小时内vWf值未升高（分别为+10±9%和-5±20%）。在接受普通肝素治疗的患者中检测到vWf严重升高（+87±11%），这与依诺肝素组（p = 0.0006）和聚乙二醇水蛭素组（p < 0.0001）有显著差异。在接受达肝素治疗的患者中，ΔvWf升高（+48±8%），与普通肝素组无差异（无统计学意义）。
我们证实，在不稳定型心绞痛患者中，最初48小时内vWf升高与30天时预后不良相关。此外，这里测试的四种不同抗凝治疗在vWf释放方面没有提供相同的保护，这可能具有重要的预后意义，并解释了最近临床试验中观察到的不同结果。
