Evidence Explainer · Aspirin & primary prevention
ASPREE did not lower cardiovascular events—and increased major bleeding
In selected older adults without cardiovascular disease, low-dose aspirin did not significantly reduce the trial’s cardiovascular composite. Major hemorrhage occurred more often.
Discovery, counterevidence, claim mapping, identifiers, funding, correction state and prose were reviewed before release.
Evidence at a glance
Benefit and bleeding measured in the same trial
- Study type
- Randomized, double-blind, placebo-controlled primary-prevention trial
- Studied in
- Humans
- Participants / sample
- 19,114 selected community-dwelling older adults without cardiovascular disease at enrollment
- Publication status
- Peer reviewed; no linked correction, retraction or expression of concern identified as of verification
- Outcome type
- Cardiovascular disease composite and major hemorrhage
- Evidence maturity
- Large human randomized outcome evidence over median 4.7 years
- Conflicts / funding
- Public and institutional funding; Bayer supplied aspirin and placebo in kind and was reported to have no other trial role
- Our assessment
- No significant cardiovascular-composite reduction; major hemorrhage was significantly higher
Read this first
Three takeaways
- Cardiovascular disease occurred at 10.7 events per 1,000 person-years with aspirin and 11.3 with placebo; HR 0.95, 95% CI 0.83–1.08.
- Major hemorrhage occurred at 8.6 versus 6.2 events per 1,000 person-years; HR 1.38, 95% CI 1.18–1.62.
- This was primary prevention. The result does not erase aspirin’s established role for selected people with cardiovascular disease or prior events.
Keep outcomes separate
A small numerical difference is not a demonstrated benefit
Cardiovascular composite
Fatal coronary disease, nonfatal heart attack, fatal or nonfatal stroke, or heart-failure hospitalization.
Major hemorrhage
Serious intracranial or qualifying extracranial bleeding—not every minor bleed.
Primary prevention
Participants did not have cardiovascular disease at enrollment.
Secondary prevention
People with prior events or established disease face a different evidence and treatment question.
The bottom line
In ASPREE’s selected older primary-prevention population, daily low-dose aspirin did not significantly reduce the prespecified cardiovascular composite and did increase major hemorrhage.
What researchers did
Investigators randomized 19,114 older adults to 100 mg daily enteric-coated aspirin or placebo. They adjudicated both cardiovascular outcomes and serious bleeding, allowing benefit and harm to be read from the same population and follow-up.
What they found
The cardiovascular composite rate was 10.7 versus 11.3 per 1,000 person-years; HR 0.95, 95% CI 0.83–1.08. Major hemorrhage was 8.6 versus 6.2 per 1,000 person-years; HR 1.38, 95% CI 1.18–1.62, P<.001.
How strong is the evidence?
This is large randomized evidence with adjudicated events. It supports a strong conclusion about increased major bleeding and a bounded conclusion that the trial did not demonstrate a significant cardiovascular-composite reduction.
What this does not show
A confidence interval crossing 1 is not proof of zero possible cardiovascular effect. Nor can ASPREE be generalized to people with prior heart attack, stroke or established vascular disease, who were outside its prevention setting.
Safety, guidance and conflicts
Major hemorrhage included hemorrhagic stroke, symptomatic intracranial bleeding, or qualifying extracranial bleeding requiring major care or causing death. USPSTF advises against initiating aspirin for primary prevention at age 60 or older. FDA emphasizes serious bleeding and individualized professional guidance.
What happens next
Better individualized prediction may refine who has enough cardiovascular risk to offset bleeding risk, but this article does not calculate a score. New evidence must preserve age, prior disease, dose, adherence, absolute events and bleeding definitions.
Educational boundary
Do not start, continue, stop or change aspirin because of this page. A clinician must distinguish primary from secondary prevention and consider bleeding history, other medicines and the reason aspirin was prescribed.
Primary sources
Sources, roles and limits
- ASPREE cardiovascular events and bleeding analysis
- Identifier
- PMID:30221597 · PMCID:PMC6289056 · DOI:10.1056/NEJMoa1805819 · NCT01038583
- Role
- Primary randomized cardiovascular and safety support
- Limitation
- Selected primary-prevention population; median 4.7 years.
- ASPREE registry
- Identifier
- NCT01038583
- Role
- Trial identity, eligibility and sponsor context
- Limitation
- Registration is not a clinical recommendation.
- ASPREE statistical analysis plan
- Identifier
- PMID:29111960 · DOI:10.1177/1747493017741383
- Role
- Prespecified analysis context
- Limitation
- Does not replace observed outcome data.
- USPSTF aspirin recommendation
- Identifier
- April 26, 2022
- Role
- Dated US primary-prevention context
- Limitation
- Does not instruct one person or erase secondary prevention.
- FDA aspirin facts
- Identifier
- FDA page checked August 3, 2026
- Role
- Current safety and indication context
- Limitation
- General information does not determine an individual decision.
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Disclosures and history
- August 3, 2026 — source discovery and independent verification completed before prose drafting.
- August 3, 2026 — cardiovascular, bleeding, primary/secondary-prevention, funding and guidance boundaries reviewed.
- Corrections: no linked correction, retraction or expression of concern identified for the featured records as of verification; guidance and registry records must be rechecked when this story is updated.