Circulation：真性阿司匹林药物抵抗罕见

　　美国宾夕法尼亚大学一项研究表明，对阿司匹林的药物抵抗是罕见的。该研究未能确定一例真性阿司匹林药理学抵抗。假性抗药，表现为对药物反应延迟和药物吸收的减少，可能出现在肠溶阿司匹林，但非即释型阿司匹林。研究于2012年12月3日在线发表于《循环》（Circulation）杂志。

　　小剂量阿司匹林可减少二次心肌梗死和卒中的发病率。然而，阿司匹林的耐药性可能会导致治疗失败。尽管有这种担忧，“阿司匹林抵抗”并没有明确的定义，对其发生率的估计也存在显著变化。该研究旨在评估真性阿司匹林药理学抵抗机制的一致性、稳定性和特异性表型的共同性，例如可能被解释为遗传原因。

　　研究共纳入400例健康志愿者，评估受试者对单剂量口服325 mg即释型或肠溶型阿司匹林的反应。反应参数反映了阿司匹林的分子靶标，即环氧合酶-1的活性。对有一次出现了“阿司匹林抵抗”现象的受试者进行重复测试，如果仍然存在“抵抗”，则暴露于小剂量肠溶阿司匹林（81 mg）和氯吡格雷（75 mg），持续一个星期。

　　结果表明，可变异的吸收引起了对单剂量325 mg肠溶阿司匹林高频率的显性抵抗（高达49％），但即释型阿司匹林（0％）。所有受试者在多次给药，延长给药时间间隔后均对阿司匹林有反应。受试者离体血小板也均对添加阿司匹林有所反应。

Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin

Background

Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of "aspirin resistance" has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes.

Methods and Results

Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared "aspirin resistant" on one occasion underwent repeat testing and if still "resistant" were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo.

Conclusions

Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.