Protocol
Aspirin (low-dose, primary prevention in healthy older adults)
Tested in 19,114 healthy adults aged 70 and over (ASPREE).
Grade D, tested: in a human randomized trial, the treated group did worse on the endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. graded. How to read a grade →
At a glance
This is a daily low-dose aspirin taken by healthy adults over 70 to prevent illness. A large study of over 19,000 people found that aspirin did not help them live longer without disability. It did not meaningfully lower heart attacks or strokes. It did raise serious bleeding. This finding is about healthy older people, not people who already had a heart attack.
- What was measured
- Living free of death, dementia or lasting disability, plus heart events and major bleeding, in healthy adults 70 and over.
- How big
- About 10 more people with major bleeding per 1,000 on aspirin (3.8% vs 2.8%), while the main measure, staying alive without dementia or disability, did not improve.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 30221596.
- Who it applies to
- 19,114 healthy adults aged 70 and over in Australia and the United States without heart disease, dementia or disability. People who already had a heart attack or stroke were not part of it.
- Safety
- The bleeding is the finding. This grade does not cover aspirin taken after a heart attack, stent or stroke, where stopping it suddenly raises the risk of another event.
- Compared with
- A dummy pill.
- Certainty
- Grade D, resting on: Randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect..
- What would change this grade
- Could rise to C with: Randomized, double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends., placebo-controlled trial of 100 mg aspirin. Who: Adults aged 70 and over at high cardiovascular risk and low bleeding risk, at least 5,000 per arm. Measured: Heart attack, stroke and death, with major bleeding counted. Length: At least 5 years.
- Cost
- No price recorded yet.
- Sources
- 7 studies cited on this record, listed under Sources.
Tested in 19,114 healthy adults aged 70 and over (ASPREE). Did not prolong disability-free survival, did not reduce cardiovascular events, increased major hemorrhage, and all-cause death was higher on aspirin during the trial, mostly from cancer, a finding the authors called unexpected; a decade of follow-up found no lasting death excess and no long-term benefit. Secondary prevention after an event is a different question entirely.
Why this letter
Why this gradeGrade D, tested, harm found. The reasoning, and what the grade does not cover.
Grade D on Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale.: tested, harm found. ASPREE randomized 19,114 healthy adults aged 70 and over to 100 mg aspirin daily or placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. for a median of 4.7 years. Disability-free survival, the primary endpoint The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight., was not improved, cardiovascular events were not meaningfully reduced, and major hemorrhage increased. In adjacent populations, ASCEND (diabetes) found fewer vascular events but more bleeding, and ARRIVE (moderate risk) was null with doubled gastrointestinal bleeding; neither enrolled healthy older adults. During ASPREE, all-cause death was higher on aspirin, mostly from cancer, which the investigators called unexpected; a decade of follow-up found no lasting death excess, no long-term benefit, and a persisting excess of major bleeding. The finding is not that aspirin does nothing, it is that in people who have not had an event, the bleeding it causes outweighs the events it prevents.
WHAT THIS GRADE DOES NOT COVERthis letter grades starting low-dose aspirin for PRIMARY prevention in healthy older adults. It does not grade aspirin taken after a heart attack, a stent, a stroke or a transient ischemic attack. That is secondary prevention, a different question with different trials and a different answer, and stopping it abruptly raises the risk of a further event. Nothing on this page is a basis for changing a prescribed medication, and that decision sits with the prescribing physician.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Who responds: this record's trial reading reports no subgroup that identifies who responds.
Evidence notes: randomized trial
Endpoint graded: Disability-free survival in healthy adults aged 70 and over (hard)
Last reviewed: October 2026
The trial that would change this grade.
A positive trial of this shape would move this entry to C.
Why the current trials fall short
In healthy older adults the trial found more bleeding and no gain in disability-free survival. A benefit would have to be shown in a narrower group selected for high heart risk and low bleeding risk.
Why people believe itOne human source; one published case report of benefit; three reports of harm.
The case for daily aspirin in healthy older adults is that it stops platelets clumping, the first step of a clot, and that in people who have already had a heart attack or stroke it prevents repeat events. For decades the same benefit was assumed for people without heart disease, and many older adults still take it.
What supporters point to, and what each source actually shows. None of it is enough to move this letter higher; the trial described above under Evidence wanted is what would.
- Human trial, a different usePooling 16 trials in people who already had vascular disease, aspirin cut serious vascular events by about a fifth. In the 6 prevention trials in people without it, the cut was 12 percent, with more major bleeding. PMID 19482214
A case report describes what happened to one or a few patients. It cannot show the treatment caused the change, and reports of success are published more often than reports of failure.
- A patient with gum disease and metabolic syndrome improved over 6 months when omega-3 with low-dose aspirin was added to dental cleaning. A different use, in one patient. PMID 32980834
- A 79-year-old woman on long-term low-dose aspirin had a spontaneous bleed around the spinal cord that weakened both legs and needed surgery. PMID 30656250
- A 65-year-old man taking 81 mg of aspirin a day for primary prevention had an upper stomach bleed after also taking two doses of naproxen. PMID 23386069
- A patient on 100 mg of aspirin a day had a spontaneous bleed around the spinal cord, which resolved without surgery. PMID 22792431
Searched PubMed, October 2026: 14 case report record(s) returned. 13 describe bleeding on low-dose aspirin, in the brain, spine and gut, several in pregnancy or with another drug; three are listed. One describes improvement in gum disease and is listed.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Aspirin among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Dose, form and timing
DO NOT STOP SECONDARY-PREVENTION ASPIRIN ON THE STRENGTH OF THIS PAGE. This record grades low-dose aspirin for PRIMARY prevention in healthy older adults only. If you have had a heart attack, a stent, a stroke or a TIA, you are on it for secondary prevention, a different question with different evidence, and stopping it abruptly raises the risk of a further event. That decision belongs with your physician. Current RCT Randomized controlled trial: people are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. evidence (ARRIVE, ASPREE, ASCEND) does not support low-dose aspirin for primary prevention in healthy older adults: bleeding risk exceeds benefit. Under physician-directed secondary prevention, the measures are occult GI bleeding by annual FIT test, GI symptoms and any bleeding events.
Safety
The bleeding is the finding. ASPREE randomized healthy older adults to low-dose aspirin and found no cardiovascular benefit and more major hemorrhage. This record is a Route 2 D: tested, harm found. Secondary prevention after an established cardiovascular event is a different question and is not what this letter covers.
Cautions documented in human studies. Each caution on this record, sorted by what it rests on.
- Major bleeding: ASPREE found more major hemorrhage on low-dose aspirin (hazard ratio How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. 1.38) with no cardiovascular benefit in healthy older adults (PMID 30221597 PMID 30221596)
- All-cause mortality: ASPREE found higher mortality (hazard ratio 1.14), driven by cancer deaths, with no lasting excess in extended follow-up (PMID 30221595 PMID 41043446)
- 3 published case reports of harm, described in the record's reports of harm (PMID 30656250 PMID 23386069 PMID 22792431)
- Stopping aspirin suddenly after a heart attack, stent or stroke raises the risk of another event, a separate question from this grade
None recorded.
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 122 · October 2026 · Corrected.
The record cited only the ASPREE mortality report, McNeil 2018 (PMID 30221595), and attributed the disability-free survival and bleeding results to it. Those come from the companion papers by the same group, now cited: McNeil 2018 (PMID 30221596), the primary endpoint report, and McNeil 2018 (PMID 30221597), the cardiovascular and bleeding report. The mortality finding is stated as the paper states it: higher all-cause death, mostly cancer, called unexpected by the authors, and not confirmed over the decade of follow-up in Wolfe 2025 (PMID 40796244) and Shah 2025 (PMID 41043446), which found no long-term benefit, a higher event rate after stopping, and persisting bleeding. ASCEND, Bowman 2018 (PMID 30146931), and ARRIVE, Gaziano 2018 (PMID 30158069), are now cited and described as the different populations they are. Letter unchanged.PMID 30221595 PMID 30221596 PMID 30221597 PMID 40796244 PMID 41043446 PMID 30146931 PMID 30158069
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- August 2026. By a language model (AI-assisted reading), not yet reviewed by a clinician.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
The evidence, in fullSeven papers, each linked to its PubMed record.
ASPREE, three companion reports: McNeil et al. (N Engl J Med, 2018; PMID 30221596), the primary endpoint, disability-free survival, not improved (21.5 versus 21.2 events per 1,000 person-years, hazard ratio 1.01), with major hemorrhage higher; McNeil et al. (N Engl J Med, 2018; PMID 30221597), cardiovascular disease not reduced (hazard ratio 0.95, 95% CI 0.83 to 1.08) and major hemorrhage up 38 percent (8.6 versus 6.2 per 1,000 person-years); McNeil et al. (N Engl J Med, 2018; PMID 30221595), all-cause mortality higher on aspirin (hazard ratio 1.14, 95% CI 1.01 to 1.29), mostly cancer deaths, which the authors call unexpected and to be interpreted with caution. Extended follow-up: Wolfe et al. (Eur Heart J, 2025; PMID 40796244), no long-term benefit on major cardiovascular events over the trial and 4.3 post-trial years (hazard ratio 1.04), a higher event rate in the post-trial period after stopping (1.17), and a persisting excess of major hemorrhage (1.24); Shah et al. (Lancet Healthy Longev, 2025; PMID 41043446), no effect on disability-free survival over almost a decade and no lasting death excess. Adjacent populations, neither healthy older adults: ASCEND (Bowman et al., N Engl J Med, 2018; PMID 30146931), 15,480 adults with diabetes, serious vascular events down 12 percent, major bleeding up 29 percent; ARRIVE (Gaziano et al., Lancet, 2018; PMID 30158069), 12,546 adults at moderate risk, null on its primary endpoint with gastrointestinal bleeding doubled, funded by Bayer. ASPREE was funded by the National Institute on Aging. D Route 2: tested, harm found.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
aspirin[tiab] AND ("primary prevention"[tiab]) AND (older[tiab] OR elderly[tiab] OR ASPREE[tiab]) AND (randomized controlled trial[pt] OR meta-analysis[pt])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the search behind this grade has been added to PubMed since October 2026.
Last run October 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
Disclosure
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
Educational use only · Not medical advice · © Evidence Based Longevity, Inc. All rights reserved · Privacy · Disclosure · Terms · Accessibility · Clinical trials
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →