Aspirin and Antiplatelet Medications (cont.)
What is aspirin resistance?
Aspirin resistance can be defined as the lack of
antiplatelet effect despite therapeutic doses of aspirin (75mg-150mg/day for at least five days). This lack
of anti-platelet response to aspirin increases the risk of developing heart
attacks, strokes, and related deaths. Aspirin resistance is different from other
causes of aspirin failure (see above), such as patient non-compliance or drug
interference from concomitant use of ibuprofen.
Some scientists believe that a segment of the population
is resistant to the antiplatelet effect of aspirin. In these aspirin-resistant
individuals, aspirin does not inhibit the formation of thromboxane A-2.
Resistant individuals can be identified in research settings by finding high
levels of 11-dehydrothromboxane B2 (a metabolic breakdown product of thromboxane
A-2) in the urine while taking
aspirin. These individuals have a higher risk of heart attack and strokes than
subjects with lower urine levels of 11-dehydrothromboxane B2.
Another way of identifying aspirin resistance in research settings is by
optical platelet aggregation. Aspirin nonresponders identified by this method
were found to have higher rates of heart attacks, strokes, and death than
aspirin responders.
What is in the future for the research on aspirin resistance?
While research scientists are increasingly convinced that
aspirin resistance exists, there are no reliable and standardized tests that
doctors in clinical practice can use to diagnose this condition. Large scale
controlled studies are needed to validate and standardize laboratory tests of aspirin resistance, and
link these tests results to clinical outcomes.
Clinical trials will also be needed to determine how best to treat aspirin
resistance. For example, should patients diagnosed as having aspirin resistance
be treated with higher doses of aspirin? Should they be treated with aspirin in
combination with another anti-platelet agent? Or should they be treated with a
different anti-platelet agent, such as clopidogrel bisulfate (Plavix)?
References:
U.S. Preventive Services Task Force; "Aspirin for the Prevention of Cardiovascular Disease: U.S. Preventive Services Task Force Recommendation Statement;" Annals of Internal Medicine; 17 March 2009. Volume 150 Issue 6. Pages 396-404.
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group (1988), "Randomized Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither Among 17 187 Cases of Suspected Acute Myocardial Infarction: ISIS-2", The Lancet 332: 349-360
Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA, Jablonsky G, Kostuk WJ, Melendez LJ, Myers MG, et al.; "Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial." N Engl J Med. 1985 Nov 28;313(22):1369-75.
Theroux P; Ouimet H; McCans J; Latour JG; Joly P; Levy G; Pelletier E; Juneau M; Stasiak J; deGuise P; et al. "Aspirin, heparin, or both to treat acute unstable angina." Journal of Medicine Vol. 319:1105-1111
LC Wallentin; "Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. Research Group on Instability in Coronary Artery Disease in Southeast Sweden"J Am Coll Cardiol, 1991; 18:1587-1593
C. H. Hennekens, MD; M. L. Dyken, MD; V. Fuster, MD. "Aspirin as a Therapeutic Agent in Cardiovascular Disease;" Circulation. 1997;96:2751-2753
Previous contributing author: Dennis Lee, M.D.
Last Editorial Review: 4/3/2009
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