Aspirin "resistance".
Recent clinical studies have shown that the expected antiplatelet effect of aspirin is not always achieved. From the laboratory point of view, resistance to aspirin is the inability to achieve the expected inhibition of platelet cyclooxygenase-(COX-)1 with prevention of platelet thromboxane (TX) A2 formation. The failure to prevent atherothrombotic events (treatment failure) must be distinguished from aspirin resistance. Nevertheless, different definitions of aspirin resistance complicate the assessment of published data, a problem aggravated by discordant results of the available diagnostic laboratory techniques.The pharmacological mechanisms of aspirin resistance are not completely understood. Potential causes include pharmacokinetic and pharmacodynamic issues, such as reduced bioavailability, increased platelet turnover, interactions with nonsteroidal anti-inflammatory drugs, comorbidities (hypercholesterolemia or diabetes mellitus), alternative pathways of platelet activation, and genetic polymorphisms. Clinical trials demonstrated a negative impact of aspirin resistance on the clinical outcome: an about fourfold increased risk of major atherothrombotic events has been found in aspirin nonresponders suffering from vascular disease.An individualized antiplatelet therapy with aspirin will have to consider the possibility of aspirin resistance. Thus, standardized and inexpensive diagnostic assays are needed. The identification of aspirin-resistant patients is essential to individually tailor antiplatelet treatment. For example, increasing the dosage of aspirin or alternative antiplatelet drugs are potential therapeutic concepts, but these require careful future investigation.
Zimmermann
Norbert
N
Federal Institute of Pharmaceutical Agents and Medicinal Products, Bonn, Germany.
Weber
Artur-Aron
AA
Hohlfeld
Thomas
T
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D003328:Coronary Thrombosis / Q000209:etiology* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006801:Humans; D010818:Practice Patterns, Physicians' / Q000639:trends; D015607:Stents / Q000009:adverse effects*
D001241:Aspirin