Schulman S P, Goldschmidt-Clermont P J, Topol E J, Califf R M, Navetta F I, Willerson J T, Chandra N C, Guerci A D, Ferguson J J, Harrington R A, Lincoff A M, Yakubov S J, Bray P F, Bahr R D, Wolfe C L, Yock P G, Anderson H V, Nygaard T W, Mason S J, Effron M B, Fatterpacker A, Raskin S, Smith J, Brashears L, Gottdiener P, du Mee C, Kitt M M, Gerstenblith G
Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md, USA.
Circulation. 1996 Nov 1;94(9):2083-9. doi: 10.1161/01.cir.94.9.2083.
Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina.
Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms.
Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.
尽管阿司匹林对不稳定型心绞痛患者有益，但它是一种相对较弱的血小板聚集抑制剂。本研究在227例不稳定型心绞痛患者中评估了抑制血小板纤维蛋白原受体糖蛋白（GP）IIb/IIIa的依替巴肽对动态心电图监测缺血发作频率和持续时间的影响。
患者接受静脉肝素和标准缺血治疗，并随机分为口服阿司匹林加安慰剂依替巴肽组；安慰剂阿司匹林加低剂量依替巴肽组（先静脉推注45微克/千克，然后以0.5微克·千克⁻¹·分钟⁻¹持续输注）；或安慰剂阿司匹林加高剂量依替巴肽组（先静脉推注90微克/千克，然后以1.0微克·千克⁻¹·分钟⁻¹持续输注）。研究药物持续使用24至72小时，并进行动态心电图监测。随机分配至高剂量依替巴肽组的患者在输注研究药物的24小时内，动态心电图监测到的缺血发作次数为0.24±0.11次（均值±标准误），持续时间为8.41±5.29分钟。随机分配至阿司匹林组的患者缺血发作次数更多（1.0±0.33次，P<.05），持续时间更长（26.2±9.8分钟，P=.01），高于高剂量依替巴肽组。停用研究药物后未发现反弹性缺血的证据。在46例患者中，依替巴肽能以剂量依赖方式迅速抑制血小板聚集。临床事件数量较少，三个治疗组之间在出血方面无差异。
静脉注射依替巴肽耐受性良好，是一种有效的血小板聚集可逆抑制剂，与阿司匹林相比，在全剂量肝素基础上加用依替巴肽可减少不稳定型心绞痛患者动态心电图监测的缺血事件数量和持续时间。
