Identifying determinants of variability to tailor aspirin therapy

Abstract

Once-daily, low-dose aspirin is a cornerstone in the prophylaxis and treatment of cardiovascular diseases. Aspirin ‘resistance’ still lacks definition, a standardized reference assay, underlying mechanisms, clinical impact or efficacy of alternative antiplatelet drugs. Aspirin response in several studies has been measured by different platelet function tests, not always reflecting aspirin pharmacodynamics, thus generating significantly heterogeneous results. The EMA indicated serum thromboxane B₂ as the only valid surrogate assay to study different aspirin formulations. Rather than resistance, recent studies focused on sources of intra- and inter-individual variability in response to aspirin, based on pharmacokinetic and/or pharmacodynamic mechanisms. Drug interactions, diabetes, conditions of increased platelet output, obesity and aging can potentially increase the variability of aspirin response. Preliminary studies testing different aspirin regimens showed that twice-daily low doses were more effective than once-daily higher aspirin doses on surrogate end points of platelet inhibition. Large studies are needed to test new disease-tailored, low-dose aspirin regimens.

Keywords::

• aspirin
• COX
• drug resistance
• eicosanoids
• personalized medicine
• platelets
• thromboxane
• variability

Acknowledgements

The authors thank Prof. Carlo Patrono for invaluable advice and challenging discussions.

Financial & competing interests disclosure

This work was supported in part by a grant from the European Union’s Seventh Framework Program (FP7/2007–2013) for the Innovative Medicine Initiative under grant agreement number IMI/115006 (the SUMMIT consortium). B Rocca has received speaker fees from Shire and AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.