From the Guidelines
Aspirin is primarily eliminated from the body through hepatic metabolism, with its effects on platelets lasting for the life of the cell, approximately 10 days, due to irreversible inhibition of cyclo-oxygenase 1. The mechanism of aspirin elimination involves the liver converting aspirin to salicylic acid, which is then further metabolized and excreted through the kidneys.
- The half-life of aspirin varies depending on the dose, with low doses having a shorter half-life compared to higher doses.
- Factors such as age, liver function, kidney function, and dose can affect aspirin's elimination, with elderly patients and those with hepatic or renal impairment experiencing delayed elimination 1.
- The effects of aspirin on vascular endothelial cells are of shorter duration compared to platelets, as endothelial cells can recover cyclo-oxygenase synthesis 1. The understanding of aspirin elimination is crucial for appropriate dosing, especially in patients with organ dysfunction or when administering multiple doses, to minimize the risk of adverse effects such as bleeding 1.
From the Research
Aspirin Elimination Mechanism
- Aspirin's antithrombotic action is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX) at the functionally important amino acid serine529 2
- This prevents the access of the substrate (arachidonic acid) to the catalytic site of the enzyme at tyrosine385 and results in an irreversible inhibition of platelet-dependent thromboxane formation 2
Aspirin Elimination and Platelet Biology
- Aspirin is an approximately 150- to 200-fold more potent inhibitor of the (constitutive) isoform of the platelet enzyme (COX-1) than the (inducible) isoform (COX-2) which is expressed by cytokines, inflammatory stimuli, and some growth factors 2
- The optimum dose of aspirin as an antithrombotic drug can differ in different organ circulations, and any effective antiplatelet dose of aspirin is associated with an increased risk of bleeding 2
Clinical Applications of Aspirin Elimination
- Aspirin has historically been one of the most important drugs in cardiology and has long been the cornerstone of antiplatelet therapy 3
- Although its role in acute coronary syndrome remains undisputed, emerging data suggest that reappraisal of the efficacy of long-term ASA in some primary and secondary prevention may be warranted 3
- Aspirin may provide an alternative for extended VTE prophylaxis, but its risk-benefit profile remains unclear, and careful patient selection remains crucial 4
Aspirin Pharmacology
- Aspirin protects against atherothrombosis while increasing the risk of major bleeding 5
- Aspirin's benefit does not outweigh its risk for primary CVD prevention in large population settings 5
- Aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come 6