Aspirin and Antiplatelet Medications (cont.)

Allergy to aspirin is a rare condition in which a patient can develop swelling of tissues, spasm of the airways (bronchospasm) that causes difficulty breathing, and even anaphylaxis, a life-threatening condition. Clearly, patients with a history of allergy to aspirin should not take aspirin. Since aspirin is related chemically to the other NSAIDs, patients who are allergic to the other NSAIDs, such as ibuprofen (Motrin) and naproxen (Aleve), also should not take aspirin.

What interactions might aspirin have with other medications?

Aspirin may interact with other medications and cause undesirable side effects. For example:

  • Aspirin, when taken together with an anti-coagulant such as warfarin (Coumadin) or enoxaparin (Lovenox), can greatly impair the body's ability to form blood clots, resulting in excessive bleeding spontaneously, from ulcers, or related to a procedure. Therefore, patients on such combinations must be closely monitored by a doctor.

  • Aspirin can raise levels of uric acid in the blood and may need to be avoided in patients with increased uric acid levels or gout.

  • Aspirin can increase the effect of medications used for lowering blood sugar levels in patients with diabetes, resulting in abnormally low blood sugar levels (hypoglycemia). Blood sugar levels may need to be more closely monitored.

  • Certain NSAIDs, particularly ibuprofen (Motrin, Advil), if taken just before aspirin or in multiples doses each day, can reduce the anti-platelet effects of aspirin and theoretically render aspirin less effective in preventing heart attacks and ischemic strokes. The ibuprofen molecule is believed to adhere to the COX-1 enzyme, thus keeping aspirin from reaching the enzyme.

What can be done to reduce the risk of ulcers from long-term aspirin use?

Long-term low dose aspirin use is generally safe. An estimated 10% of the patients taking long-term aspirin (75-325 mg/day) can develop ulcers. Most of these ulcers were asymptomatic (no abdominal pain or bleeding). Patients at a higher risk of developing ulcers with low dose aspirin included elderly patients age 70 years and older, and patients with H. pylori stomach infection (see below). The risk of significant ulcer bleeding from aspirin is low (approximately 1%). One can reduce the risk of bleeding by adding a daily dose of a proton pump inhibitor for example, pantoprazole (Protonix), esomeprazole (Nexium), rabeprazole (Aciphex), or lansoprazole (Prevacid, Prevacid SoluTab), and omeprazole (Prilosec, Zegerid).

Chronic H. Pylori infection of the stomach is found in up to 30% of adults in the U.S. Patients with gastritis due to H. pylori will have a higher risk of bleeding when given aspirin or NSAIDs long-term. Eradication of H. pylori from the stomach with antibiotics can reduce the risk of bleeding from chronic aspirin use.

Buffered and coated aspirin do not seem to have any beneficial effect in preventing ulcers and ulcer bleeding.

What are the limitations of aspirin treatment?

Aspirin is not always effective in preventing strokes and heart attacks. Examples of possible causes of aspirin failure include:

  • Poor patient compliance (not taking the medication regularly)

  • Inadequate dosing

  • Concurrent intake of other NSAIDs such as ibuprofen that interferes with the anti-platelet action of aspirin

  • Activation of platelet aggregation via pathways not blocked by aspirin

  • Aspirin resistance

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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