The Lowdown on Low-Dose Aspirin for Primary Prevention
Pivotal Randomized Trials and Guidelines
It’s hard to turn around a medical myth, exemplified by the notion that low-dose aspirin is safe and effective in healthy adults for primary prevention of heart disease, especially in people aged 60 years and older. In 2018, 3 pivotal, very large randomized trials were published, consistently showing the risk of major bleeding exceeded the benefit of CV event reduction. Even though it has now been >7 years since these trials were published, a substantial proportion of people of advanced age are still taking low-dose aspirin for primary prevention, mostly as advised by their physicians! In a survey of 160,000 Americans without heart disease, more than 30% of people age 70+ years were taking low-dose aspirin in 2021.
In this post, I’ll review the relevant data for low-dose aspirin, including some nuances, the guidelines, longer follow-up, and the question of use for cancer prevention.
The 3 Pivotal Trials
A summary Table of the wealth of new data from 3 randomized, placebo-controlled mega-trials published in 2018.
ASPREE assessed aspirin in a healthy elderly population (mean age 74) of 19,114 participants from Australia and the United States. There were 1,052 deaths during nearly 5 years of follow-up, with a 14% higher rate of death for aspirin (all-cause mortality) mostly accounted for by increased cancer mortality (3.1% vs 2.3%, a 31% increased hazard ratio). There was no significant reduction of cardiovascular events for aspirin, which was dosed at 100 mg enteric-coated. Aspirin significantly increased major bleeding rates with rates of 8.6 events per 1,000 person-years in the aspirin group versus 6.2 per 1,000 person-years in the placebo group (HR, 1.38; P<0.001), a nearly 40% higher risk, primarily driven by gastrointestinal and intracranial bleeds.
Here is a graphic summary of the major outcomes in ASPREE as I published in SUPER AGERS.
ASCEND was a primary prevention trial in people with diabetes, a key risk factor, but no evident cardiovascular disease. A total of 15,480 participants with mean age of 63 years were followed for 7.4 years. As shown below, the 12% reduction of vascular events was offset by a 29% excess of major bleeding events. The conclusion of the trial report was was follows: “The absolute lower rates of serious vascular events were of similar magnitude to the absolute higher rates of major bleeding, even among participants who had a high vascular risk.”
ARRIVE enrolled 12,546 participants deemed at moderate risk for cardiovascular disease, age 55+ for men, 60+ for women, and followed for 5 years and found no benefit for reduction of enteric-coated aspirin time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischemic attack (shown below). There was about a doubling of gastrointestinal bleeding events.
Long-Term Follow-Up of ASPREE
The ASPREE trial was most relevant for extrapolating to healthy people of advanced age, without diabetes. Fortunately, there was extended follow-up for 15,668 participants another 4.3 years after the primary report. This revealed a 17% increase in major adverse cardiovascular events and 8% increased of major bleeding events for the low dose aspirin group vs placebo, respectively. The cumulative results for the full extent of follow-up are shown below. MACE is major adverse cardiovascular event.
Revised Guidelines
These trials led to the ACC/AHA and the US Preventive Services Task Force (USPSTF) to change their recommendations for low-dose aspirin.
Here are the ACC/AHA guidelines summarized:
And the USPSTF guidelines:
You can see the contraindication for use of low-dose aspirin by both guidelines, with a cutoff of age 70+ for ACC/AHA and age 60+ by USPSTF. The lower age for the latter was backed up extensively by updated modeling in 2022.
What About Special Risk Factors?
Two risk factors that are frequently asked about are high coronary artery calcium scores by CT (CAC) and high blood levels of LP(a). There are no data to support primary prevention of low-dose aspirin for elevated Lp(a) in people of advanced age, although this is a recognized risk factor for atherothrombotic events.
The ACC/AHA guidelines addressed high calcium scores from the MESA cohort results: elevated CAC score can be used to reclassify risk and guide the personalized allocation of aspirin for adults aged 40 to 70, but there is no indication for use for age 70+. In the MESA cohort, not a randomized trial, the numbers needed to treat for CAC of 100 and 400 are shown below over 5 years to prevent 1 event. 400 people are needed to treat for 5 years with a CAC of 400 or higher to prevent 1 event. That is the basis for the ACC/AHA recommendation of low dose aspirin for people age <70 years. It is not nearly as well backed up as the data from the 3 pivotal randomized trials.
Lessons from President Trump
A lengthy interview with President Trump about his health was published in WSJ, reporting that his doctors advised taking 81 mg of aspirin to prevent heart disease but he takes 325 mg. He explained: “They say aspirin is good for thinning out the blood, and I don’t want thick blood pouring through my heart. I want nice, thin blood pouring through my heart. Does that make sense?”
No, it doesn’t make any sense! Aspirin reduces platelet aggregation (clumping); it’s not a blood thiner. Blood thinners are drugs that work on the clotting proteins such as Coumadin or Apixiban (Eliquis). Trump is 78 and shouldn’t be taking aspirin at any dose for primary prevention, even with an elevated CAC of 140 that was reported in 2018. Added to that is his unwillingness to accept his physician recommendations, which are not evidence-based and that too is concerning.
Cancer Prevention
There has been a longstanding debate about whether low-dose aspirin should be used to prevent cancer, especially of the colon. in older adults. The ASPREE trial of healthy aged participants helped to understand the benefit of aspirin for primary prevention of cancer. Recall that the trial found higher cancer-related mortality, which is certainly not favorable. But best estimates showed 100 mg aspirin provided some modest protection from developing cancer (Figure).
Of note, that benefit was linked to having clonal hematopoiesis of indeterminate origin (CHIP, blood stem cell clones), with a variant allele fraction (VAF) of 10% or higher, a frequent finding in people of advanced age (>10% by age 70), but one that we do not assay in medical practice! As I previously reviewed, CHIP increase is linked with the risk of blood and other cancers, and cardiovascular events.
That needs to be assessed prospectively, but there may well be a group of healthy elderly who would benefit from low-dose aspirin if we assayed CHIP or other biomarkers of high-risk for cancer.
Concluding Remarks
The body of evidence reviewed here strongly argues against use of low-dose aspirin for people of older age (be it 60+ or 70+) for primary prevention—without heart disease. Without cardiovascular disease means no prior heart attack, bypass surgery, or percutaneous coronary intervention (i.e. stent) since these represent secondary prevention, which has clearcut net benefit for aspirin. That benefit extends for secondary prevention of cerebrovascular disease (TIA, stroke) individualized for the basis of risk of major bleeding.
Beyond the review of the data, it is notable that 7 years after these pivotal trials were published, the medical community is not fully aware of the data. As mentioned in the opening paragraph, the latest available data suggests 1 of 3 healthy Americans age 70+ are still taking low-dose aspirin for primary prevention, as suggested by their physicians. There’s a much lesser percentage taking aspirin by their own choice. (Figure).
The recent article about President Trump’s aspirin self-dosing has helped to put the aspirin story back into the spotlight. I hope this edition of Ground Truths helps get the proper evidence out there. It is striking to me how hard it is to change the practice of medicine, and how long it takes, even when we have such a solid basis.
Thanks to Ground Truths subscribers (approaching 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026
There was an interview with me about what I eat and what I avoid in the Washington Post today. If you’re interested here is a gift link.
It was great to see that SUPER AGERS was selected by a big non-fiction book club readers as the second favorite book for 202
Well, the President may not do so, but I, at soon-to-be age 77, WILL follow your advice, precisely because it is evidence-based. Thank you for keeping us up to speed on this and so many other issues. My very best wishes to you and yours for the New Year.
I had been taking low dose aspirin for several years but when the studies came out my primary care physician told me to stop taking it. In January 2024 I had a heart attack (99% blockage in left anterior descending artery), a stent was put in place and I was put on statins to lower cholesterol and blood thinners for a year as well as back on low dose aspirin. After I was taken off blood thinners I was kept on the low dose aspirin which seems to be recommended based on your reporting(I am 66 years old). Thank you for the easy to understand explanation of the studies, especially in light of the president's recent wacky statements about his aspirin regiment.