What do current guidelines say about aspirin for primary prevention?
The most authoritative US guideline, from the US Preventive Services Task Force (USPSTF) updated in 2022, recommends against starting low-dose aspirin for primary prevention in adults aged 60 or older (a 'D' recommendation) [6]. For adults aged 40-59 who have a 10% or greater 10-year cardiovascular disease (CVD) risk, the decision should be an individual one, with a small net benefit possible for those not at increased bleeding risk (a 'C' recommendation) [6]. This represents a significant shift from earlier, more permissive guidance.
The 2019 American College of Cardiology/American Heart Association guidelines similarly state that aspirin may be considered (Class IIb) only for patients aged 40-70 at higher CVD risk, and that routine use should be avoided in those over 70 (Class III:Harm) [4]. A large registry study found that immediately before these 2019 guidelines, over one-quarter of patients on aspirin for primary prevention were using it inappropriately (e.g., under 40 or over 70) or without a recommended indication [4].
What does the evidence show about the benefits and harms?
The largest meta-analysis included here, pooling 15 randomized controlled trials with over 165,000 participants, found that aspirin reduced nonfatal heart attacks by 18% and ischemic strokes by 13%, but increased major bleeding by 50%, intracranial bleeding by 32%, and major gastrointestinal bleeding by 52% [5]. Importantly, aspirin did not reduce all-cause death or cardiovascular death [5]. Another meta-analysis of 11 trials (134,470 participants) found a 10% reduction in major cardiovascular events but a 44% increase in major bleeding, with no significant effect on cardiovascular or all-cause mortality [1].
The net benefit is small and highly dependent on individual risk. For example, in the ASPREE trial of healthy adults aged 70 and older, aspirin reduced major adverse cardiovascular events by only 1.7 events per 1,000 person-years while increasing clinically significant bleeding by the same amount — essentially a wash [3]. This is why guidelines now recommend against starting aspirin in older adults [6].
Are there any groups who might still benefit from aspirin?
Yes, but the evidence is limited and specific. One study found that older individuals (≥70) with elevated lipoprotein(a) genotypes — a genetic marker of higher cardiovascular risk — appeared to get a larger benefit from aspirin, with a reduction of 11.4 MACE events per 1,000 person-years without a significant increase in bleeding [3]. However, this is a subgroup analysis from a single trial and needs confirmation.
For people with diabetes, the picture is especially uncertain. A review notes that recent large trials failed to show a net benefit with standard once-daily low-dose aspirin in patients with diabetes, possibly because diabetes alters platelet function and aspirin metabolism [7]. The authors suggest that twice-daily dosing or non-enteric-coated formulations might be more effective, but properly powered trials are lacking [7].
Importantly, East Asian populations appear to have a higher bleeding risk with aspirin. A meta-analysis found that while aspirin reduced cardiovascular events similarly in East Asians and Westerners, the risk of major bleeding was significantly higher in East Asians (relative risk 2.48 vs. 1.45), driven by a more than threefold increase in gastrointestinal bleeding [2]. This means the net harm may be greater in East Asian patients, and aspirin should be prescribed even more cautiously [2].
About These Sources
This answer is built on 7 peer-reviewed studies — published from 2020 to 2023, 6 in Q1 journals, collectively cited 716 times — selected as the most relevant from 11 studies that passed quality screening, drawn from 48 papers retrieved from a database of over 500 million.
Sources used in this answer
Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer
In a meta-analysis of 11 RCTs (134,470 participants), low-dose aspirin reduced major cardiovascular events by 10% but increased major bleeding by 44%, with no significant reduction in cardiovascular or all-cause mortality [1].
Low-Dose Aspirin for Primary Prevention of Cardiovascular Events Comparing East Asians With Westerners
In a meta-analysis comparing East Asians (2 RCTs, 17,003 participants) with Westerners (9 RCTs, 117,467 participants), aspirin similarly reduced MACE but caused significantly more major bleeding in East Asians (RR 2.48 vs. 1.45), especially gastrointestinal bleeding (RR 3.29 vs. 1.56) [2].
Aspirin for Primary Prevention of Cardiovascular Events in Relation to Lipoprotein(a) Genotypes
In the ASPREE trial of 12,815 genotyped adults ≥70, aspirin reduced MACE by 1.7 events per 1,000 person-years but increased bleeding by the same amount; however, in those with elevated lipoprotein(a) genotypes, aspirin reduced MACE by 11.4 events per 1,000 person-years without significantly increased bleeding [3].
Potential Impact of the 2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease Recommendations on the Inappropriate Routine Use of Aspirin and Aspirin Use Without a Recommended Indication for Primary Prevention of Cardiovascular Disease in Cardiology Practices: Insights From the NCDR PINNACLE Registry
In a US registry of 855,366 patients from 400 cardiology practices, 27.6% of patients on aspirin for primary prevention were using it inappropriately (under 40 or over 70) and 26.0% without a recommended indication, with significant practice-level variation [5].
Aspirin for Primary Prevention of Cardiovascular Events.
In a meta-analysis of 15 RCTs (165,502 participants), aspirin reduced nonfatal MI by 18% and ischemic stroke by 13%, but increased major bleeding by 50%, intracranial bleeding by 32%, and major GI bleeding by 52%, with no reduction in all-cause or cardiovascular death [9].
Aspirin Use to Prevent Cardiovascular Disease
The 2022 USPSTF recommendation states that initiating aspirin for primary prevention has a small net benefit in adults aged 40-59 with ≥10% 10-year CVD risk (C recommendation), and no net benefit in adults aged 60 or older (D recommendation) [10].
Aspirin for Primary Cardiovascular Prevention in Patients with Diabetes: Uncertainties and Opportunities
A review of aspirin for primary prevention in diabetes notes that recent large trials failed to show net benefit with once-daily low-dose aspirin, possibly due to altered platelet function and faster platelet turnover in diabetes, and suggests that twice-daily or non-enteric-coated formulations may be more effective [11].