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Drug Insight: aspirin resistance—fact or fashion?

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 42–50 (2007)Cite this article

An Article Report to this article was published on 01 March 2007

An Article Report to this article was published on 01 March 2007

Abstract

The term aspirin resistance has been used increasingly in clinical studies. The aim of this Review is to analyze the origin of this term, to discuss the biochemical, functional and clinical correlates of the phenomenon and to offer a conceptual framework to redefine the major determinants of variability between individuals in response to aspirin. Awareness needs to be increased of factors that might interfere with the desired antiplatelet effect of aspirin, particularly in terms of patients' adherence to treatment and avoidable drug interactions with some traditional NSAIDs. Gaining such knowledge could result in improved care of patients and might avoid the requesting of unnecessary platelet function tests of unproven clinical significance.

Key Points

  • Drug resistance generally implies a change of the drug target and can be detected by a specific laboratory test, the results of which have a direct impact on whether drug therapy should be changed

  • Aspirin resistance seems, by contrast, to be indicated by incomplete inhibition of platelet function fluctuating over time and to be partly reversible with increasing aspirin dose

  • Testing for aspirin resistance and changing therapy on the basis of laboratory tests is currently not recommended because of a lack of data on the efficacy and safety of this strategy

  • Variability between individuals in response to low-dose aspirin is determined partly by pharmacodynamic interactions with some traditional NSAIDs and aspirin-insensitive sources of thromboxane biosynthesis

  • Increased awareness of the factors potentially limiting the antiplatelet effect of aspirin, particularly patients' adherence to therapy and drug interactions, could improve the clinical efficacy and safety of low-dose aspirin

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Figure 1: The change in optical density (TMAX) of the primary phase of the platelet aggregation response induced by ADP (2.5 µmol/l, 5.0 µmol/l, and 10.0 µmol/l) ex vivo in five volunteers before receiving aspirin (control period), on the seventh day of each dosage period and 7 days after the last dose.
Figure 2: Acetylation of cyclo-oxygenase-1 (A), inhibition of platelet thromboxane production (B) and reduction of vascular death (C) by low-dose aspirin.
Figure 3: Maximum biosynthetic capacity of human platelets and in vivo thromboxane biosynthesis in healthy individuals.
Figure 4: The risk of vascular complications is the major determinant of the absolute benefit of preventive strategies.

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Acknowledgements

The authors are supported by grants from the Italian Ministry of University and Research (FIRB Project RBNE 01A882) and the European Union (EICOSANOX Project LSHM-CT-2004-005033) to the Center of Excellence on Aging of the “G. d'Annunzio” University Foundation. The expert editorial assistance of Laura Di Benedetto and Daniela Basilico is gratefully acknowledged.

Author information

Authors and Affiliations

  1. C Patrono is Professor of Pharmacology, and B Rocca is Adjunct Professor of Pharmacology, in the 2nd Medical School of the University of Rome “La Sapienza”, Rome, Italy.,

    Carlo Patrono & Bianca Rocca

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  1. Carlo Patrono
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  2. Bianca Rocca
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Corresponding author

Correspondence to Carlo Patrono.

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Competing interests

Carlo Patrono received lecture and consulting fees for AstraZeneca, Bayer AG, Eli Lilly, Nicox, sanofi-aventis and Servier. Bianca Rocca has received lecture fees from Nycomed.

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Patrono, C., Rocca, B. Drug Insight: aspirin resistance—fact or fashion?. Nat Rev Cardiol 4, 42–50 (2007). https://doi.org/10.1038/ncpcardio0728

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