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他汀类药物与阿司匹林合用降低心血管疾病高危患者抗血小板作用的变异性。

Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of Statins in High-Risk Patients for Cardiovascular Disease.

机构信息

Department of Neuroscience, Imaging and Clinical Sciences.

CeSI-MeT, "G. d'Annunzio" University, Chieti, Italy.

出版信息

Clin Pharmacol Ther. 2018 Jul;104(1):111-119. doi: 10.1002/cpt.1075. Epub 2018 Apr 19.

Abstract

We studied the influence of cardiovascular (CV) risk factors, previous CV events, and cotreatments with preventive medicines, on residual platelet thromboxane (TX)B production in 182 patients chronically treated with enteric coated (EC)-aspirin (100 mg/day). The response to aspirin was also verified by assessing arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB levels. Residual serum TXB levels exceeded the upper limit value for an adequate aspirin response in 14% of individuals. This phenomenon was detected at 12 hours after dosing with aspirin. The coadministration of statins (mostly atorvastatin) was an independent predictor of residual serum TXB levels, and the percentage of patients with enhanced values was significantly lower in statin users vs. nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB generation by increasing the extent of acetylation of platelet COX-1 by aspirin. In conclusion, the coadministration of statins may counter the mechanisms associated with reduced bioavailability of aspirin detected in some individuals with CV disease.

摘要

我们研究了心血管(CV)危险因素、既往 CV 事件以及与预防药物的联合治疗对 182 例长期接受肠溶阿司匹林(100mg/天)治疗的患者的血小板血栓素(TX)B 产生的残留影响。通过评估花生四烯酸诱导的血小板聚集和尿 11-脱氢-TXB 水平来验证阿司匹林的反应。在 14%的个体中,残留血清 TXB 水平超过了阿司匹林反应充分的上限值。这种现象在服用阿司匹林 12 小时后被检测到。他汀类药物(主要是阿托伐他汀)的联合使用是残留血清 TXB 水平的独立预测因子,且在他汀类药物使用者中,具有增强值的患者比例明显低于非使用者。我们提供了体外证据表明,阿托伐他汀通过增加阿司匹林对血小板 COX-1 的乙酰化程度来减少残留 TXB 的生成。总之,他汀类药物的联合使用可能会对抗在一些患有 CV 疾病的个体中检测到的与阿司匹林生物利用度降低相关的机制。

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