Peptide & Experimental

Aspirin for prevention (primary prevention)

Q: Does daily aspirin protect healthy people from heart attack and stroke?

Not demonstrably in the ASPREE trial of 19,114 healthy people aged 70 and over. Cardiovascular disease occurred at 10.7 versus 11.3 events per 1,000 person-years, hazard ratio 0.95, without a clear difference. Major bleeding, by contrast, was at 8.6 versus 6.2 events per 1,000 person-years.

Q: Is it true that more people died on aspirin?

Yes. In ASPREE, 12.7 people per 1,000 person-years died on aspirin and 11.1 on placebo, hazard ratio 1.14. Cancer deaths accounted for the largest share. This breakdown was post hoc and exploratory; the authors call the result unexpected and to be interpreted with caution.

Q: Does this also apply after a heart attack or stroke?

No. After a heart attack or stroke, the benefit of aspirin is established and undisputed. Anyone taking it for this reason or on medical instruction does not stop it on their own, but discusses this with their doctor first.

Q: What side effects does aspirin for prevention have?

The most important harm is bleeding. In ASPREE, major bleeding occurred in 3.8 percent on aspirin and 2.8 percent on placebo, hazard ratio 1.38. On top of that came higher all-cause mortality with a hazard ratio of 1.14.

Q: What do the guidelines recommend?

Aspirin is approved and established in secondary prevention after a heart attack or stroke. For prevention in healthy people, the guidelines have largely advised against it since the 2018 ASPREE trial. Whether it makes sense in an individual case is a decision for a doctor.

Q: What is the ASPREE trial?

ASPREE is the largest randomized trial of aspirin in healthy older people. It assigned 19,114 people aged 70 and over without cardiovascular disease, dementia or disability to daily 100 mg aspirin or placebo. After a median of 4.7 years it was stopped early because no benefit on the primary goal could be expected any more.

Platelet aggregation inhibitor (COX-1 inhibitor), low dose · ASA 100, low-dose acetylsalicylic acid

After a heart attack or stroke, the benefit of low-dose aspirin is established and undisputed; this page expressly does not apply to that situation. For prevention in healthy people, the question has been studied just as thoroughly and answered: the largest trial in people aged seventy and over found no benefit on the primary goal, but more major bleeding and higher all-cause mortality than placebo.

What aspirin for prevention is

This means the daily intake of low-dose acetylsalicylic acid by people without cardiovascular disease, that is, as a precaution, before anything has happened. The technical term is primary prevention. It must be distinguished from secondary prevention after a heart attack or stroke: there the benefit is established, and this page changes nothing about that.

What is rated is the state of knowledge. Aspirin is cheap, available everywhere and has been in use for decades. For prevention in healthy people, a large randomized trial is available. That is why the negative finding is also reliable: here the data are not missing, here they come out against the practice.

How it works

Acetylsalicylic acid irreversibly inhibits the enzyme COX-1 in the platelets and thereby lowers the formation of thromboxane A2. The platelets clump together less easily, and the tendency to clot decreases. The most important harm follows from the same mechanism: the risk of bleeding rises.

The mechanism explains why aspirin can protect after a vascular occlusion. Whether the protection in healthy people outweighs the price paid in bleeding is a question it does not answer. That had to be settled by a trial.

What is well supported

After a heart attack or stroke, the benefit is established. In secondary prevention, aspirin is approved and established. Anyone who takes it for this reason is not who this page is about.
The question of prevention has been studied properly. ASPREE randomized 19,114 people aged 70 and over (Black and Hispanic people in the US aged 65 and over) without cardiovascular disease, dementia or physical disability to daily 100 mg enteric-coated aspirin or placebo. The median age was 74 years, 56.4 percent were women, and the median follow-up was 4.7 years.
The result on the primary goal is clear. The primary endpoint of death, dementia and persistent disability occurred at 21.5 versus 21.2 events per 1,000 person-years, HR 1.01 (95 percent confidence interval 0.92 to 1.11), p = 0.79. The trial was stopped early because no benefit could be expected if it continued.
Long experience, known risk profile. Aspirin has been used for decades. The tendency to bleed is the best-known and most important harm of the substance and was measured precisely once again in ASPREE.

What the studies show

ASPREE: no gain in healthy years of life

McNeil 2018 (NEJM) reports the primary result. Among 19,114 people, the rate of death, dementia and persistent disability was 21.5 events per 1,000 person-years on aspirin and 21.2 on placebo, hazard ratio 1.01 (0.92 to 1.11), p = 0.79. Major bleeding occurred in 3.8 versus 2.8 percent, hazard ratio 1.38 (1.18 to 1.62), p<0.001. In the last year of the trial, 62.1 percent of the aspirin group and 64.1 percent of the placebo group took the tablets as intended.

All-cause mortality: higher instead of lower

The second analysis (McNeil 2018, NEJM) looks at the 1,052 deaths. On aspirin, 12.7 people per 1,000 person-years died, on placebo 11.1, hazard ratio 1.14 (1.01 to 1.29). Cancer deaths accounted for the largest share of the difference, with 1.6 additional deaths per 1,000 person-years: 3.1 versus 2.3 percent, hazard ratio 1.31 (1.10 to 1.56). The breakdown by cause of death was post hoc and exploratory; the authors themselves call the result unexpected and to be interpreted with caution.

Cardiovascular disease and bleeding

The third analysis (McNeil 2018, NEJM) tested what aspirin is taken for as a preventive measure. Cardiovascular disease occurred at 10.7 versus 11.3 events per 1,000 person-years, hazard ratio 0.95 (0.83 to 1.08), that is, without a clear difference. Major bleeding was at 8.6 versus 6.2 events per 1,000 person-years, hazard ratio 1.38 (1.18 to 1.62), p<0.001.

What the numbers mean in absolute terms

In absolute terms, these rates result in about 2.4 additional major bleeds and 1.6 additional deaths per 1,000 person-years on aspirin. The differences were calculated from the event rates; for the difference between relative and absolute effect, see the glossary (German). None of the three endpoints shows a gain that outweighs this price.

Where the data stop

The cancer signal. The higher cancer mortality comes from a post hoc, unplanned analysis of causes of death. The authors regard it as unexpected and to be interpreted with caution. This does not show that aspirin causes cancer deaths. The planned bleeding finding and the absence of a benefit on the primary goal stand independently of it.
Younger healthy people. ASPREE enrolled people aged 70 and over, in some groups 65 and over. For younger healthy people, the trial makes no direct statement.
Full adherence. In the last year of the trial, only a little over six in ten participants took their tablets as intended. The analysis therefore reflects the everyday reality of a trial, not uninterrupted intake.
The long term. The trial was stopped early after a median of 4.7 years. What happens over considerably longer periods is not described by these three analyses.

Status, approval and legal

Aspirin is approved and established in secondary prevention after a heart attack or stroke. For primary prevention in healthy people, the guidelines have largely advised against it since ASPREE (NEJM 2018).

ASPREE tested daily 100 mg enteric-coated acetylsalicylic acid. That is the trial dose, not a recommendation. Whether aspirin makes sense in an individual case is a decision for a doctor.

Safety

Bleeding is the best-known and most important harm. In ASPREE, the rate of major bleeding on aspirin was 8.6 versus 6.2 events per 1,000 person-years, hazard ratio 1.38, p<0.001. On top of that came the higher all-cause mortality with a hazard ratio of 1.14.

The safety value in the BK-Score refers expressly to use in healthy people. After a heart attack or stroke the opposite applies; there the established benefit prevails.

Not starting is different from stopping. Anyone taking aspirin after an event or on medical instruction does not stop it on their own, but discusses this with their doctor first.

BK-Score Well studied – effect not confirmed

Human evidence		10
Mechanism		9
Safety data		4
Hype gap		5
Track record of use		10

For prevention in healthy people, the question has been answered, and the answer is no. ASPREE (NEJM 2018) randomized 19,114 people aged seventy and over without heart attack, stroke, dementia or disability to 100 mg enteric-coated aspirin or placebo; median age 74, median 4.7 years, stopped early. On the primary endpoint of death, dementia and persistent disability, the result was 21.5 versus 21.2 events per thousand person-years (HR 1.01; p = 0.79). All-cause mortality was higher on aspirin (HR 1.14), and there was more major bleeding on top. The safety value refers expressly to this use in healthy people. After a heart attack or stroke the opposite applies – there the benefit is established and this entry does not apply.

The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)

Frequently asked questions about aspirin for prevention (primary prevention)

Does daily aspirin protect healthy people from heart attack and stroke?