Analyzing the Risks and Benefits of Aspirin

Question: What is the appropriate use of aspirin therapy for patients with diabetes?

Answer: People with diabetes face an increased risk for thrombotic vascular events. Platelet reactivity plays a key role in thrombosis, particularly at the site of an unstable plaque. In diabetes, there is increased platelet reactivity and excess production of thromboxane by platelets. This is a prostaglandin metabolite that causes vasoconstriction and platelet aggregation and thereby contributes to thrombotic events. Aspirin, even in low doses, blocks thromboxane production by inactivating a key enzyme in its synthesis.

Many studies of antiplatelet agents in people with or without vascular disease have been conducted.^1,2 The American Diabetes Association recommends 75–162 mg/day aspirin for secondary prevention in adult men and women with diabetes with evidence of cardiovascular disease and for primary prevention in high-risk men and women >40 years with type 1 or 2 diabetes.³ High-risk characteristics include a family history of coronary heart disease, hypertension, cigarette smoking, LDL cholesterol > 100 mg/dl and dyslipidemia, and albuminuria.

Most type 2 diabetes patients are eligible for aspirin therapy under these guidelines. This is also true if one uses the American Heart Association guidelines for a risk for myocardial infarction >10% over a 10-year period.⁴

ASPIRIN THERAPY ISSUES

Some concerns that arise when considering prescribing aspirin therapy to patients with diabetes include risk of bleeding, treatment failure, and effectiveness for women.

Serious gastrointestinal (GI) bleeding may occur, and the risk is doubled with aspirin therapy. GI bleeding risk is dose-related with aspirin doses >325 mg/day.

In two trials focused on aspirin use in high-risk patients with diabetes, researchers found a significant reduction in the risk for myocardial infarction (28–36%).^5,6 These mixed primary and secondary prevention studies established that aspirin did not lead to excessive retinal bleeding or to increased cerebral hemorrhage in treated hypertensive patients.

A new concern is that of aspirin resistance or, more accurately, treatment failure. This is best defined as the occurrence of a major vascular event, such as myocardial infarction, that occurs in someone who is treated regularly with aspirin. The mechanism involved in vascular thrombosis in aspirin-treated individuals is not known.

Data on aspirin's preventive effects are limited for women. The only large study of women found that 100 mg of aspirin every other day had no effect on myocardial infarction but reduced the risk for thrombotic stroke by 24%.⁷

In summary, low-dose aspirin is recommended for adult patients with diabetes who are at high cardiovascular risk. There is adequate evidence that the benefits of lowering the risk of myocardial infarction in men and thrombotic stroke in women outweigh the risk of serious GI bleeding. ▪