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L.2.04.401
Aspirin is a mainstay in the prevention of atherosclerotic events. Physicians have other drugs available to replace or supplement aspirin, principal of these being clopidogrel (Plavix®). It is fortunate that there are aspirin alternatives because recent research indicates that there are patients who are resistant to aspirin, and even to clopidogrel.
Both aspirin and clopidogrel inhibit the ability of blood platelets to aggregate, or clump. Clumping is one of the early steps in producing a blood clot, which is, under ordinary circumstances, a beneficial effect. Inappropriate clot formation, however, in the arteries supplying blood to the heart or brain, impairs blood flow, leading to damage or death of tissue.
Aspirin is an antiplatelet drug that works to prevent heart attacks and strokes by reducing the production of thromboxane, the chemical that makes platelets sticky. Although thromboxane cannot be measured directly, its chemical biomarker, 11-dehydro-thromboxane B2, can. A low level of this biomarker in the urine means that aspirin is working as it should to reduce thromboxane production. High levels of the biomarker in the patient’s urine may mean that the dosage of aspirin is not effective for decreasing the risk of a heart attack or stroke for that particular patient.
Aspirin's ability to suppress the production of prostaglandins and thromboxanes (both of which are produced during the metabolism of aspirin or clopidogrel) is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks. A dose of 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostacyclin synthesis being little affected. However, higher doses of aspirin are required to attain further inhibition.
Despite aspirin’s remarkable benefits, approximately 10-20% of aspirin-treated patients will have a cardiovascular event within five years of initiating therapy. This led to the concept that there is a subset of “aspirin resistant” patients who do not respond to aspirin clumping therapy and are therefore at persistent risk of future cardiovascular events. The term "aspirin resistance" has been used to describe the occurrence of occlusive cardiovascular disease (CVD) events despite regular intake of this agent at recommended doses. True biochemical aspirin resistance must be differentiated from non-compliance, a more common reason for therapy failure.
It is difficult to assess the clinical importance of aspirin resistance since there is currently no consensus on how to define, measure, and treat aspirin and clopidogrel resistance. Laboratory tests are just becoming available, and test results can vary depending on the laboratory performing the test and which test system is used. As a result, the incidence of ‘resistance’ has been estimated to be as low as 5% in some studies, and as high as 60% in others. This variation probably also reflects differences in treatment dosage and duration, as well as the existence of other conditions and/or medications that might influence drug action.
The lack of standardized measures of platelet function makes estimation of the prevalence of aspirin resistance difficult. Mounting evidence suggests that aspirin resistance is associated with adverse clinical outcomes, which have been assessed in patients with coronary artery disease, myocardial infarction, cerebrovascular disease and peripheral vascular disease. Patients with aspirin resistance have significantly more adverse vascular events than patients without such resistance. However, there are no guidelines for the treatment of aspirin resistance.
Aspirin resistance testing is considered investigational.
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The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
05/01/2013: New policy added. Approved by Medical Policy Advisory Committee.
07/06/2015: Code Reference section updated for ICD-10.
06/07/2016: Policy number L.2.04.401 added. Investigative definition updated in Policy Guidelines section.
11/21/2019: Policy description updated. Policy statement unchanged. Sources updated.
08/21/2023: Policy reviewed; no changes.
08/20/2024: Policy reviewed; no changes.
Blue Cross Blue Shield of Michigan medical policy, Aspirin Resistance Testing
Code Number | Description |
CPT-4 | |
84431 | Thromboxane metabolite(s), including thromboxane if performed, urine |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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