Results Summary
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.
Professional Abstract
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
| Design Element | Description |
|---|---|
| Design | Randomized controlled trial |
| Population | 15,076 people with atherosclerotic cardiovascular disease |
| Interventions/ Comparators |
|
| Outcomes | Primary: composite cardiovascular outcome including all-cause mortality, hospitalization for non-fatal myocardial infarction, and hospitalization for non-fatal stroke; and hospitalization for major bleeding associated with a blood product transfusion Secondary: coronary revascularization including percutaneous coronary intervention or coronary artery bypass graft; individual components of composite outcome, including all-cause mortality and hospitalization for non-fatal myocardial infarction, non-fatal stroke, or transient ischemic attack |
| Timeframe | Up to 4-year follow-up for primary outcome |
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.
Final Research Report
View this project's final research report.
Journal Citations
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- Reviewers expressed concern about the lack of diversity among participants in this large and complex pragmatic study and asked the researchers to consider how to improve on this in the future. The researchers acknowledged that the lack of participant diversity affected the generalizability of the study but noted that this lack of diversity was often present in clinical research because of factors such as patient interest and historical mistrust.
- Reviewers asked for additional missing details to be added to the report regarding the statistical analysis plan, including handling of missing data, the size of the interaction effect in subgroup analyses and information about sensitivity and per-protocol analyses. The researchers expanded their methods section to incorporate this information so that it matched the information provided in the results section.
- Reviewers asked for clarification about the planned subgroup analyses conducted in this study because very little was included about the planned analyses in the methods section. The researchers provided more information about the planned subgroups in the methods section to mirror the results section describing subgroup effects. The researchers also noted that they were able to expand the diversity of participants by allowing for participation without using the online patient portal. The researchers expressed concern that without such expansion in recruitment, the patient sample would have been healthier with lower changes of death or hospitalization due to cardiovascular disease.
In relation to recruitment, the reviewers noted that in the study evaluation description it was clear that the face-to-face method for participant recruitment was more successful than the use of email or portal communications. The reviewers wondered whether this method would be feasible for other clinical trials given the considerable staff and cost burden. The researchers acknowledged this concern and explained that it has been discussed in multiple forums but there are no definitive strategies to overcome such recruitment problems.
Conflict of Interest Disclosures
Project Information
Key Dates
Study Registration Information
*Matthew Roe, MD, MHS was the original Principal Investigator on the project.