Goldschmidt-Clermont P J, Schulman S P, Bray P F, Chandra N C, Grigoryev D, Dise K R, Sagar M, Fox R J, Coleman L D, Richardson C, Dorsey F C, du Mee C, Kitt M M, Ouyang P, Baughman K L, Gerstenblith G
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Clin Cardiol. 1996 Nov;19(11):869-74. doi: 10.1002/clc.4960191106.
Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men.
We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men.
To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina.
We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin.
Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.
尽管女性通常比男性晚数年发生冠状动脉疾病，但一旦出现症状性疾病，其血栓栓塞并发症比男性更严重。血栓栓塞事件后介导这种性别差异结果的机制尚不清楚。我们之前研究了早发冠状动脉疾病患者兄弟姐妹的血小板功能。我们观察到女性的血小板比男性的血小板反应性更高。特别是，用各种激动剂体外刺激的女性血小板比男性血小板结合更多的纤维蛋白原分子。
我们假设在急性冠状动脉事件患者中，控制血小板活性在女性中可能比在男性中需要更强的拮抗剂。
为了验证这一假设，我们回顾性研究了一项关于依替巴肽治疗不稳定型心绞痛的试验结果。
我们报告，与标准血小板抑制剂阿司匹林相比，使用特异性糖蛋白IIb-IIIa抑制剂依替巴肽治疗的不稳定型心绞痛女性患者，血小板聚集和动态心电图检测到的缺血发作显著减少。相比之下，使用包括阿司匹林在内的标准治疗的不稳定型心绞痛男性患者，血小板聚集和动态心电图检测到的缺血事件均得到良好控制。
依替巴肽确实为男性提供了保护，但与女性不同的是，其保护作用不超过阿司匹林所能达到的效果。我们的数据与以下概念一致，即女性的血小板需要更强、更特异性的抑制剂来限制其活性，并且血小板在急性冠状动脉综合征女性中可能比男性发挥更重要的作用。最重要的是，特异性糖蛋白IIb-IIIa抑制剂可能是一种治疗选择，它在女性中对缺血事件的抑制作用与在冠状动脉疾病男性中一样有效。
