Saw Jacqueline, Madsen Esben Hjorth, Chan Sammy, Maurer-Spurej Elisabeth
Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Canadian Blood Services, Vancouver, British Columbia, Canada.
J Am Coll Cardiol. 2008 Dec 2;52(23):1826-1833. doi: 10.1016/j.jacc.2008.08.047.
This study was designed to evaluate the effects of long-term clopidogrel and aspirin administration on platelet aggregation, activation, and inflammation.
Clopidogrel resistance was described in 15% to 30% of patients with short-term therapy, but its antiplatelet effects with long-term therapy is unknown.
We performed a prospective study of patients undergoing coronary stenting who were on aspirin for > or =5 days but not previously on clopidogrel. Clopidogrel 600 mg was given before stenting. Clopidogrel 75 mg/day and aspirin 325 mg/day were continued for 1 year. Light-transmittance aggregometry with 5-micromol/l adenosine diphosphate and 1-mmol/l arachidonic acid stimulation; VerifyNow clopidogrel and aspirin assays; platelet activation receptor expression of CD40L, CD62P, and PAC-1 (antibody against activated glycoprotein IIb/IIIa); and inflammatory markers of soluble CD40L and P-selectin, high-sensitivity C-reactive protein, interleukin-10, and interleukin-18 were measured at baseline; 1 day; and 1, 6, and 12 months. Our primary analysis compared light-transmittance aggregometry aggregation at 1 versus 12 months.
We enrolled 26 patients who completed a 1-year follow-up. Maximal platelet adenosine diphosphate-stimulated aggregation was 61.8 +/- 25.9% at baseline, 22.1 +/- 18.3% at 1 day, 30.6 +/- 16.8% at 1 month, 29.0 +/- 13.3% at 6 months, and 26.7 +/- 13.6% at 12 months (p = 0.099 for 12 months vs. 1 month). VerifyNow clopidogrel platelet inhibition was similar at 12 months versus 1 month (38.9 +/- 19.7% vs. 45.6 +/- 26.7%, p = 0.578). Likewise, there was no difference in aspirin's effects on platelet aggregation at 12 months versus 1 month. In contrast, platelet activation receptor expression of CD40L, CD62P, and PAC-1 were higher at 12 months versus 1 month.
Our pilot study showed no attenuation of clopidogrel's effects on platelet aggregation with long-term administration. However, platelet activation receptor expression increased with time and should be further evaluated.
本研究旨在评估长期服用氯吡格雷和阿司匹林对血小板聚集、活化及炎症的影响。
短期治疗的患者中，15%至30%存在氯吡格雷抵抗，但长期治疗的抗血小板效果尚不清楚。
我们对接受冠状动脉支架置入术且已服用阿司匹林≥5天但此前未服用氯吡格雷的患者进行了一项前瞻性研究。在支架置入术前给予氯吡格雷600mg。氯吡格雷75mg/天和阿司匹林325mg/天持续服用1年。采用5μmol/L二磷酸腺苷和1mmol/L花生四烯酸刺激的透光率聚集法；VerifyNow氯吡格雷和阿司匹林检测；检测血小板活化受体CD40L、CD62P和PAC-1（活化糖蛋白IIb/IIIa抗体）的表达；以及可溶性CD40L和P-选择素、高敏C反应蛋白、白细胞介素-10和白细胞介素-18等炎症标志物，分别在基线、1天、1、6和12个月时进行检测。我们的主要分析比较了1个月和12个月时的透光率聚集法聚集情况。
我们纳入了26例完成1年随访的患者。基线时血小板二磷酸腺苷刺激的最大聚集率为61.8±25.9%，1天时为22.1±18.3%，1个月时为30.6±16.8%，6个月时为29.0±13.3%，12个月时为26.7±13.6%（12个月与1个月相比，p = 0.099）。VerifyNow氯吡格雷对血小板的抑制作用在12个月和1个月时相似（38.9±19.7%对45.6±26.7%，p = 0.578）。同样，阿司匹林在12个月和1个月时对血小板聚集的作用也没有差异。相比之下，12个月时血小板活化受体CD40L、CD62P和PAC-1的表达高于1个月时。
我们的初步研究表明，长期服用氯吡格雷对血小板聚集的作用没有减弱。然而，血小板活化受体表达随时间增加，应进一步评估。
