Ault K A, Cannon C P, Mitchell J, McCahan J, Tracy R P, Novotny W F, Reimann J D, Braunwald E
Maine Medical Center Research Institute, South Portland 04106, USA.
J Am Coll Cardiol. 1999 Mar;33(3):634-9. doi: 10.1016/s0735-1097(98)00635-4.
This study was designed to determine the magnitude and time course of platelet activation during therapy of acute coronary syndromes with an oral platelet antagonist.
Platelet activation and aggregation are central to the pathogenesis of the acute coronary syndromes (ACS). However, few data are available on levels of platelet activation over time in patients with ACS, especially in the setting of chronic glycoprotein (GP) IIb/IIIa inhibition.
The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind trial evaluating the effects of sibrafiban, an oral, selective antagonist of the platelet glycoprotein IIb/IIIa receptor in patients stabilized after an ACS. A subset of 90 of the 329 patients in the study had measurement of platelet activation as assessed by the expression of platelet associated P-Selectin on days 0, 7 and 28. Platelet activation was measured in blood samples that were fixed either immediately (spontaneous activation) or after 5 minute incubation with 0, 1 microM or 5 microM ADP in order to assess platelet responsiveness to very low or moderate stimulation.
At baseline there was a significant elevation of spontaneous platelet activation as compared to samples obtained from normal donors or from patients who did not have acute coronary syndromes (ACS patients 27.6+/-18.7%, Normal controls 8.5+/-4.4%, Patient controls 10.9+/-7.1%, p < 0.005 for both). In addition, there was a significant decrease in the levels of platelet activation with time during the 28 days of treatment with sibrafiban. Nevertheless, even on day 28, the TIMI-12 patients continued to show elevated platelet activation in comparison to the control groups (p < 0.05 for both).
These results suggest that platelets remain activated long after clinical stabilization post ACS. Although platelet activation decreased after one month of oral GPIIb/IIIa inhibition, levels remained higher than normal, suggesting the need for long-term antiplatelet therapy following ACS.
本研究旨在确定口服血小板拮抗剂治疗急性冠脉综合征期间血小板活化的程度和时间进程。
血小板活化和聚集是急性冠脉综合征（ACS）发病机制的核心。然而，关于ACS患者血小板活化水平随时间变化的数据很少，尤其是在慢性糖蛋白（GP）IIb/IIIa抑制的情况下。
心肌梗死溶栓（TIMI）12试验是一项II期双盲试验，评估西拉非班（一种口服的血小板糖蛋白IIb/IIIa受体选择性拮抗剂）对ACS后病情稳定患者的影响。该研究中329例患者的90例子集在第0、7和28天通过血小板相关P-选择素的表达评估血小板活化情况。在立即固定（自发活化）或与0、1 microM或5 microM ADP孵育5分钟后的血样中测量血小板活化，以评估血小板对极低或中等刺激的反应性。
与从正常供体或无急性冠脉综合征患者获得的样本相比，基线时自发血小板活化显著升高（ACS患者27.6±18.7%，正常对照8.5±4.4%，患者对照10.9±7.1%，两者p<0.005）。此外，在西拉非班治疗的28天期间，血小板活化水平随时间显著降低。然而，即使在第28天，TIMI-12患者与对照组相比仍显示血小板活化升高（两者p<0.05）。
这些结果表明，ACS临床稳定后血小板仍长期处于活化状态。虽然口服GPIIb/IIIa抑制一个月后血小板活化降低，但水平仍高于正常，提示ACS后需要长期抗血小板治疗。
