Drug Resistance and Pseudoresistance
Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA (2013)
Circulation 127(3): 377-385.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Grosser, TiloUniBi
;
Fries, Susanne;
Lawson, John A.;
Kapoor, Shiv C.;
Grant, Gregory R.;
FitzGerald, Garret A.
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Alternativer Titel
An Unintended Consequence of Enteric Coating Aspirin
Abstract / Bemerkung
**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 the molecular target of aspirin, cyclooxygenase-1. Individuals who appeared aspirin resistant on 1 occasion underwent repeat testing, and if still resistant were exposed to low-dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for 1 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 on repeated exposure, extension of the postdosing 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.
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 the molecular target of aspirin, cyclooxygenase-1. Individuals who appeared aspirin resistant on 1 occasion underwent repeat testing, and if still resistant were exposed to low-dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for 1 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 on repeated exposure, extension of the postdosing 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.
Erscheinungsjahr
2013
Zeitschriftentitel
Circulation
Band
127
Ausgabe
3
Seite(n)
377-385
ISSN
0009-7322
eISSN
1524-4539
Page URI
https://pub.uni-bielefeld.de/record/2965322
Zitieren
Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug Resistance and Pseudoresistance. Circulation. 2013;127(3):377-385.
Grosser, T., Fries, S., Lawson, J. A., Kapoor, S. C., Grant, G. R., & FitzGerald, G. A. (2013). Drug Resistance and Pseudoresistance. Circulation, 127(3), 377-385. https://doi.org/10.1161/CIRCULATIONAHA.112.117283
Grosser, Tilo, Fries, Susanne, Lawson, John A., Kapoor, Shiv C., Grant, Gregory R., and FitzGerald, Garret A. 2013. “Drug Resistance and Pseudoresistance”. Circulation 127 (3): 377-385.
Grosser, T., Fries, S., Lawson, J. A., Kapoor, S. C., Grant, G. R., and FitzGerald, G. A. (2013). Drug Resistance and Pseudoresistance. Circulation 127, 377-385.
Grosser, T., et al., 2013. Drug Resistance and Pseudoresistance. Circulation, 127(3), p 377-385.
T. Grosser, et al., “Drug Resistance and Pseudoresistance”, Circulation, vol. 127, 2013, pp. 377-385.
Grosser, T., Fries, S., Lawson, J.A., Kapoor, S.C., Grant, G.R., FitzGerald, G.A.: Drug Resistance and Pseudoresistance. Circulation. 127, 377-385 (2013).
Grosser, Tilo, Fries, Susanne, Lawson, John A., Kapoor, Shiv C., Grant, Gregory R., and FitzGerald, Garret A. “Drug Resistance and Pseudoresistance”. Circulation 127.3 (2013): 377-385.
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