下肢动脉硬化闭塞症患者阿司匹林抵抗率的真实世界研究

Prevalence of biological aspirin resistance in patients with arteriosclerosis obliterans: a real-world study

摘要:

背景与目的 临床实践中，部分下肢动脉硬化闭塞症（ASO）患者在规范服用阿司匹林后仍发生血栓相关事件，常被笼统归因于“阿司匹林抵抗”，但真实的生物学抵抗发生率及其影响因素尚不明确。不同检测方法与判定标准的差异，使既往研究报道的阿司匹林抵抗率差异显著，增加了临床决策的不确定性。本研究基于花生四烯酸（AA）诱导的血小板聚集试验，评估真实世界ASO患者阿司匹林生物学抵抗的实际发生率，并分析其与年龄、性别等人口学因素的关系，为正确理解“阿司匹林治疗失败”及优化临床应对策略提供循证依据。方法 采用回顾性、单中心横断面研究设计，纳入2022年1月—2025年8月中南大学湘雅医院血管外科规律服用阿司匹林肠溶片100 mg/d的ASO患者597例。通过AA诱导的血小板最大聚集率（MAR）评估阿司匹林反应性，定义MAR≥20%为阿司匹林抵抗。比较不同年龄及性别组间差异，并以多因素Logistic回归分析阿司匹林抵抗的相关因素。结果 597例患者中检出阿司匹林抵抗16例，总体抵抗率为2.68%。不同年龄组（≤50岁、>50~60岁、>60~70岁、>70岁）阿司匹林抵抗率分别为4.31%、2.12%、2.42%和2.50%，组间差异无统计学意义（P=0.505）。男性与女性抵抗率分别为3.17%和2.24%，差异亦无统计学意义（P=0.686）。多因素Logistic回归分析显示，年龄和性别均不是阿司匹林抵抗的独立预测因素（均P>0.05）。结论 在真实世界ASO患者中，基于AA诱导血小板聚集试验测得的阿司匹林生物学抵抗率极低，且与年龄和性别无显著相关性。临床实践中所谓的“阿司匹林治疗失败”多为伪性抵抗，面对治疗失败时应优先评估服药依从性、剂型与吸收、药物相互作用及剂量匹配等可干预因素，而非常规进行阿司匹林抵抗筛查。

Abstract:

Background and Aims In clinical practice, some patients with arteriosclerosis obliterans (ASO) experience thrombotic events despite regular aspirin therapy, a phenomenon often broadly attributed to "aspirin resistance." However, the true prevalence of biological aspirin resistance and its associated factors remain unclear. Marked heterogeneity in reported resistance rates across studies has resulted mainly from differences in testing methods and diagnostic criteria, leading to uncertainty in clinical decision-making. This study aimed to determine the real-world prevalence of biological aspirin resistance in ASO patients using an arachidonic acid (AA)–induced platelet aggregation assay and to explore its associations with age and sex, thereby providing evidence for the appropriate interpretation of aspirin treatment failure.Methods This retrospective, single-center, cross-sectional study included 597 ASO patients who regularly received enteric-coated aspirin (100 mg/d) at Xiangya Hospital, Central South University, between January 2022 and August 2025. Aspirin resistance was assessed using the AA-induced maximum aggregation rate (MAR), with resistance defined as MAR ≥20%. Differences among age and sex groups were analyzed, and independent predictors were identified using multivariate Logistic regression.Results Among the 597 patients, 16 cases of aspirin resistance were detected, with an overall resistance rate of 2.68%. The resistance rates in different age groups (≤50 years old, >50 to 60 years old, >60 to 70 years old, and >70 years old) were 4.31%, 2.12%, 2.42%, and 2.50%, respectively, and there was no statistically significant difference among the groups (P=0.505). The resistance rates in males and females were 3.17% and 2.24%, respectively, and the difference was also not statistically significant (P=0.686). Multivariate Logistic regression analysis showed that neither age nor gender was an independent predictor of aspirin resistance (all P>0.05).Conclusion The prevalence of true biological aspirin resistance in ASO patients is very low and is not associated with demographic characteristics. Most cases of clinically perceived aspirin treatment failure are likely attributable to pseudo-resistance. Clinical management should prioritize the evaluation of modifiable factors such as medication adherence, formulation and absorption, drug interactions, and dose adequacy rather than routine screening for aspirin resistance.