Dr. Williams is a PGY-1 pharmacy resident and Dr. Isaac is a clinical assistant professor of pharmacy at Xavier University of Louisiana College of Pharmacy in New Orleans.
Aspirin is one of the most widely used OTC drugs. Its anti-inflammatory and antipyretic effects make it beneficial for use in the treatment of mild-to-moderate pain and fever. The antiplatelet effects of low-dose aspirin also make it effective for the pri-mary and secondary prevention of cardiovascular disease and stroke. Aspirin supplementation also has been linked with beneficial effects in various cancers and Alzheimer’s disease.1
Considering the number of established and emerging uses of aspirin, patients may have questions concerning the beneficial ef-fects of its use. It is important that pharmacists are aware of the many uses of aspirin and are able to provide appropriate informa-tion about the benefits and risks.
Primary Prevention of Cardiovascular Disease and Stroke
An estimated 36% of US adults take aspirin regularly for cardiovascular disease and stroke prevention.2 The US Preventive Ser-vices Task Force (USPSTF) published a recent update to their recommendations for the use of aspirin for the primary prevention of cardiovascular disease. The USPSTF recommends the use of low-dose aspirin in men aged 45 to 79 and women aged 55 to 79 when the benefit of a reduction in myocardial infarction in men or ischemic stroke in women outweighs the risk of gastrointestinal (GI) bleeding.3
The USPSTF provides recommendations for aspirin use according to sex due to evidence suggesting that aspirin may have dif-ferential effects in men and women. Evidence suggests the benefits of aspirin use for primary prevention are derived from a reduc-tion in myocardial infarction in men and a reduction in ischemic stroke in women.3-5 Consequently, before making a recommenda-tion to initiate low-dose aspirin in individuals without a history of coronary heart disease (CHD) or stroke, it is important to assess CHD risk in men and stroke risk in women.
The USPSTF provides links to online tools to assess CHD and stroke risk. There is a CHD risk calculator available at http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof, and a stroke risk calculator available at www.westernstroke.org. The CHD and stroke risk should be weighed against the risk for bleeding. Risk factors for GI bleeding include increasing age, male sex, upper GI tract pain, GI ulcers, concomitant nonsteroidal anti-inflammatory drug (NSAID) use, uncontrolled hypertension, and con-comitant use of anticoagulants.2
Table 1 provides the 10-year CHD and stroke risk levels at which the number of these events prevented by aspirin is closely balanced to the number of serious bleeding events.
This table, along with the risk calculators, can be useful when deciding whether to recommend daily low-dose aspirin therapy in an individual patient.
As the 10-year risk of CHD or stroke increases above the values listed in the table, the recommendation to take aspirin should become stronger.3 Daily low-dose aspirin is not recommended for the primary prevention of stroke in women younger than 55 years or for the prevention of myocardial infarction in men younger than 45 years of age.
The appropriate long-term daily dose of aspirin remains controversial. In clinical trials, however, doses of 75 to 81 mg/day were as effective as higher doses for cardiovascular disease prevention.2,6 Doses exceeding 81 mg are associated with an increased risk of bleeding.2,6
Cancer and Alzheimer’s Disease
Among the possible emerging uses of aspirin include the prevention of cancer and the treatment of Alzheimer’s disease.1 One trial examining the effectiveness of aspirin as a chemoprotective agent against colorectal adenomas revealed a 19% relative reduction in the risk of recurrent colorectal adenomas in patients with a history of the tumors who were randomized to receive aspirin 81 mg daily.7
The Baltimore Longitudinal Study of Aging demonstrated that aspirin might be of benefit for Alzheimer’s disease patients. Among patients with 2 or more years of aspirin use, the relative risk of Alzheimer’s disease was 0.4 (95% confidence interval, 0.2-0.8).8 The authors concluded that aspirin may reduce the inflammatory process in Alzheimer’s disease. Further research is neces-sary before recommendations can be made concerning benefits of aspirin in the prevention of cancer and the treatment of Alz-heimer’s disease.
Risks Associated with Aspirin Use
Bleeding events, including GI bleeding and hemorrhagic stroke, are the most serious adverse effects associated with daily aspirin therapy. Low-dose aspirin carries a small, but significant risk of upper GI bleeding.9 Risk factors for GI bleeding include advanced age, male sex, a history of GI ulcers, and concomitant NSAID use.3
Although small, there is a risk of hemorrhagic stroke associated with the use of low-dose aspirin for the primary prevention of CHD or stroke, with an estimated 0.2 events per 1000 patient-years.10 Risk factors for hemorrhagic stroke with chronic aspirin use include a history of intracranial hemorrhage, advanced age, and uncontrolled hypertension.10
The presence of any of the risk factors mentioned is not a contraindication for daily aspirin use. In some patients the benefits of therapy may outweigh the risk of bleeding. All patients should be informed of the risks associated with daily aspirin therapy.
Drug Interactions with Aspirin
Several drug interactions are associated with aspirin. Aspirin may increase methotrexate serum levels and may displace valproic acid from its binding site, which can result in toxicity.11,12 Concomitant use of oral anticoagulants, low-molecular-weight heparins, NSAIDs, and other antiplatelet agents can increase the risk of bleeding and GI ulceration.12
When given with ibuprofen, the potential exists for the attenuation of the antiplatelet effects of aspirin.13 Patients should be advised to take aspirin 8 hours before, or 30 minutes after, ibuprofen ingestion to avoid this potential interaction. Additionally, the effects of angiotensin-converting enzyme inhibitors may be blunted by aspirin administration, but this effect may only be significant at higher doses of aspirin.12
Patients also should be notified of herbal supplements that have antiplatelet activity, including cat’s claw, dong quai, feverfew, garlic, ginger, ginkgo- biloba, green tea, and ginseng.14
After assessing CHD and stroke risk along with risk factors for bleeding, pharmacists can assist patients in determining whether daily low-dose aspirin may be appropriate. Patients should, however, consult their physician before beginning daily aspirin therapy. Table 2 provides tips for counseling patients regarding daily low-dose aspirin therapy. Pharmacists also can provide information on the benefits as well as the risks associated with the use of daily OTC aspirin.