Comparing the Safety and Effectiveness of Low-Dose versus High-Dose Aspirin to Prevent Problems from Heart Disease -- The ADAPTABLE Study -- A PCORnet® Study

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What was the research about?

Heart disease is the leading cause of death in the United States. Doctors recommend that people with heart disease take aspirin to prevent problems, like heart attack or stroke. Questions remain about which dose of aspirin people should take to prevent problems from heart disease while limiting the risk of bleeding related to aspirin.

In this study, the research team compared the safety and effectiveness of low-dose versus high-dose aspirin among patients with heart disease. The team looked at the risks of heart-related health outcomes and the side effects of bleeding.

What were the results?

Patients who took low-dose or high-dose aspirin had a similar risk of:

• A hospital stay for a heart attack, stroke, or blood transfusion due to a bleeding problem
• Dying for any reason
• Having a stent placed in their heart or open heart surgery
• A hospital stay for a transient ischemic attack, which is a ministroke that lasts a short period of time

Who was in the study?

The study included 15,076 people with heart disease. All received care at one of 40 health centers across the country. Among patients, 80 percent were White, 9 percent were Black, 1 percent were Asian, 1 percent were American Indian or Alaska Native, 1 percent reported more than one race, and 7 percent didn’t report a race; 3 percent were Hispanic. The average age was 68, and 69 percent were men.

What did the research team do?

The research team identified patients for the study by looking at electronic health records in PCORnet®. Patients gave their consent to be in the study. Then, the team assigned patients by chance to take a low dose or a high dose of aspirin. The low dose was 81 milligrams; the high dose was 325 milligrams.

Patients had study visits online or over the phone at the start of the study, one to three weeks later, and every three or six months for up to four years. During study visits, patients answered questions about taking their aspirin dose as recommended and any hospital stays. The research team also reviewed patients’ electronic health records and insurance claims data.

Patients with heart disease helped design the study.

What were the limits of the study?

Most patients in the study were White men. Results may differ for women or people from other racial backgrounds. Among patients assigned to take high-dose aspirin, 42 percent switched to low-dose aspirin during the study. Reasons for switching may have included patient or doctor preference, bruising, or bleeding. The high number of people who switched may have made it hard to detect differences between the doses.

Future research comparing aspirin doses could include more women and people from other racial backgrounds.

How can people use the results?

Patients and their doctors can use these results when considering the dose of aspirin to take to prevent problems from heart disease.

Objective

To compare the safety and effectiveness of low-dose versus high-dose aspirin use on the risk of major cardiovascular adverse events among patients with heart disease

Study Design

This pragmatic randomized controlled trial compared the effectiveness of two daily aspirin regimens for preventing myocardial infarction, stroke, and death among patients with existing heart disease. The study also compared the risk for major bleeding. Current US guidelines do not provide a definitive recommendation on aspirin dose for patients with atherosclerotic cardiovascular disease.

Researchers identified patients for the study by searching electronic health records in PCORnet®. Following informed consent, researchers randomly assigned patients to take either 81 milligrams (mg) or 325 mg of aspirin once a day.

The study included 15,076 patients with heart disease who were receiving care at one of 40 health centers across the United States. Among patients, 80% were White, 9% were Black, 1% were Asian, 1% were American Indian or Alaska Native, 1% were multiple races, and 7% did not report a race; 3% were Hispanic, and 7% did not report an ethnicity. The average age was 68, and 69% were men.

Patients completed study visits online or by phone at study entry, again one to three weeks later, and every three or six months for up to four years. During visits, patients answered questions about whether they took their assigned dose of aspirin as directed and whether they had any hospitalizations. Researchers also used data collected from electronic health records and claims to look at patient outcomes.

Patients with heart disease helped design the study.

Results

The risk of adverse cardiovascular outcomes, by either the composite or individual measures, and the risk of hospitalization for major bleeding did not differ significantly between the aspirin dosing regimens. Among those taking 81 mg of aspirin, 7.3% died or were hospitalized for heart attack or stroke compared with 7.5% of those taking 325 mg of aspirin. Other study outcomes did not differ significantly for the two dosing regimens.

Limitations

Among patients, 42% of those assigned to the 325-mg dose switched to 81 mg, which may have made it difficult to detect differences between the doses. Reasons for switching may have included patient or doctor preference, bruising, bleeding, or the development of other illnesses. Also, most patients in the study were White men. Results may differ for women or people from other racial backgrounds.

Conclusions and Relevance

In this study, the two aspirin dosing regimens did not differ in safety and effectiveness when used to prevent major cardiovascular events.

Future Research Needs

Future research comparing the safety and effectiveness of aspirin dosing regimens could include more women and people from different racial backgrounds.