August 2025
INTRODUCTION —
Cardiovascular disease (CVD) and cancer are leading causes of morbidity and mortality worldwide [1,2]. Aspirin produces important reductions in CVD morbidity and mortality among survivors of a wide range of occlusive CVD events, especially myocardial infarction and stroke. In secondary prevention, the absolute benefits on occlusive events are far greater than the absolute risks of major bleeding. In primary prevention, however, among apparently healthy people, the benefit-to-harm ratio is less clear.
Although the benefits of aspirin on CVD have been known for decades, evidence from randomized trials also suggests a possible benefit on colorectal cancer. These findings may impact the threshold for the prescription of aspirin by health care professionals and the wishes of healthy people considering aspirin use.
This topic summarizes the evidence regarding the benefits and harms of aspirin for the primary prevention of CVD and cancer. The utilization of aspirin should be a shared decision between health care professionals and their patients that carefully weighs all the absolute benefits against the absolute risks [3-5].
Discussion of the role of aspirin in the secondary prevention of CVD is presented separately. The role of nonsteroidal anti-inflammatory drugs and aspirin in the prevention of colorectal cancer (exclusive of CVD) is also discussed separately. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer" and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)
MECHANISMS OF ACTION
●CVD – Aspirin produces an antiplatelet effect by irreversibly acetylating the active site of cyclooxygenase (COX) 1, which is required for the production of thromboxane A2, a powerful promoter of aggregation. These effects are achieved by daily doses of 75 mg (and higher) or perhaps doses as low as 30 mg. Higher doses of aspirin also inhibit COX-2, which blocks prostaglandin production, leading to analgesic and antipyretic effects. (See "NSAIDs: Therapeutic use and variability of response in adults", section on 'Dosing and duration' and "Platelet biology and mechanism of anti-platelet drugs" and "Mechanisms of acute coronary syndromes related to atherosclerosis".)
●Cancer – Plausible biologic mechanisms for anticancer effects of aspirin include induction of cell apoptosis as well as inhibition of COX-catalyzed prostaglandin production. In colorectal cancer, aspirin may also influence the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) pathway [6]. Prostaglandins are associated with tumor angiogenesis, cell proliferation, and inhibition of immune surveillance and apoptosis [7]. (See "The role of platelets in coronary heart disease" and "NSAIDs (including aspirin): Role in prevention of colorectal cancer".)
POSSIBLE BENEFITS
Summary of outcomes — Based on multiple meta-analyses [8-12] and subsequent trials [13-17], a summary of the possible benefits of aspirin on outcomes is outlined in the table (table 1). Key information in the table includes the last two columns that present the number of events in 1000 patients not receiving aspirin and the difference in those receiving aspirin. For example, in patients at low cardiovascular risk, 27 in 1000 patients (2.7 percent) not using aspirin will experience, over 10 years, a myocardial infarction (MI); this will be the case in five (0.5 percent) fewer receiving aspirin (their likelihood of infarction drops from 2.7 to 2.2 percent). The following presents a summary of the evidence in the table:
●All-cause mortality or cardiovascular mortality – No impact or a very small reduction (moderate-quality evidence)
●Nonfatal MI – Likely a reduction in nonfatal MI over 10 years (high-quality evidence)
●Nonfatal stroke – Likely no reduction or a very small reduction in nonfatal stroke over 10 years (moderate-quality evidence)
●Colon cancer incidence – Possible reduction in colon cancer incidence over long-term follow-up of 20 years (low-quality evidence)
Although meta-analyses, including a 2019 analysis that added the three large 2018 trials [13-17], have found a reduction in composite outcomes with aspirin, it is more informative to assess the potential benefits on individual outcomes independently, as outlined below [18].
All-cause mortality — In the aggregate, there is moderate-quality evidence for no more than a very small impact on mortality. In two 2019 meta-analyses of primary prevention trials, the impact of aspirin on all-cause mortality was not significant and included the possibility of both very small benefit and harm. In a meta-analysis of 13 randomized trials, aspirin did not reduce all-cause mortality, compared with no aspirin (absolute risk reduction 0.13 percent, 95% CI -0.07 to 0.32 percent) [18]. Similarly, in a meta-analysis of 11 trials, the incidence of all-cause mortality was similar between the groups randomized to aspirin (4.6 percent) and placebo (4.7 percent; relative risk [RR] 0.98, 95% CI 0.93-1.02) [19].
The 2019 meta-analyses included three large 2018 randomized trials that enrolled somewhat different populations [13-17]. One of these trials (A Study of Cardiovascular Events in Diabetes [ASCEND]) reported an effect consistent with earlier trials that suggested a small RR reduction in mortality [8-10]; a second (Aspirin to Reduce Risk of Initial Vascular Events [ARRIVE]) suggested no effect, though with a confidence interval consistent with the prior evidence; and a third (ASPirin in Reducing Events in the Elderly [ASPREE]) suggested an increase in mortality:
●In the ASCEND trial, 15,480 patients with diabetes (94 percent with type 2 diabetes) but no evidence of CVD were randomly assigned to aspirin (100 mg daily) or placebo [13]. The majority of patients were taking statins and antihypertensive medication. Over 80 percent of patients were at low to moderate risk (less than 10 percent within five years) of a CVD event (see "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'ASCVD risk assessment'). The risk of death from any cause was 9.7 versus 10.2 percent, respectively (rate ratio 0.94, 95% CI 0.85-1.04), during a mean follow-up of 7.4 years [13].
●In the ARRIVE trial, 12,546 moderate CVD risk patients (approximately 15 percent in 10 years) were randomly assigned to aspirin (100 mg daily) or placebo [17]. After a median follow-up of five years, the risk of any death was 2.55 and 2.57 percent, respectively (hazard ratio [HR] 0.99, 95% CI 0.80-1.24) [17].
●In the ASPREE trial, 19,114 individuals 70 years or older were randomly assigned to aspirin (100 mg daily) or placebo [14-16]. After a median of 4.7 years of follow-up, the risk of death from any cause was 12.7 and 11.1 events per 1000 person-years, respectively (HR 1.14, 95% CI 1.01-1.29) [16].
Cardiovascular outcomes
●Cardiovascular mortality – A 2016 meta-analysis of 11 trials that included individual patient-level data among 118,445 adults who were randomly assigned to either aspirin (at doses between 50 and 500 mg daily) or placebo found no difference in the risk of cardiovascular mortality (RR 0.97, 95% CI 0.85-1.10) [10]. Three large subsequent trials produced results consistent with prior evidence; differences in vascular or cardiovascular death were very small and consistent with chance (ASCEND [rate ratio 0.93, 95% CI 0.77-1.12], ARRIVE [HR 0.97, 95% CI 0.62-1.52], and ASPREE trial of patients 70 years of age or older [HR 0.97, 95% CI 0.71-1.33]) [13-17].
●MI – The 2016 meta-analysis described above found a 22 percent reduction in nonfatal MI with aspirin use (RR 0.78, 95% CI 0.71-0.87) [10]. Although the point estimates in three subsequent trials suggest a less beneficial impact on nonfatal MI, the results have relatively wide confidence intervals and are consistent with estimates from the 2016 meta-analysis: ASCEND (rate ratio 0.98, 95% CI 0.80-1.19), ARRIVE trial (HR 0.85, 95% CI 0.64-1.11), and ASPREE trial of patients 70 years of age or older (HR 0.93, 95% CI 0.76-1.15) [13-17].
●Stroke – Data from randomized trials have not found that aspirin convincingly reduces the risk of stroke. In a large, well-conducted primary prevention trial from 2005, aspirin reduced the risk of stroke (RR 0.82, 95% CI 0.69-0.99), compared with placebo [20].
However, the 2016 meta-analysis described above found no significant benefit on nonfatal stroke (RR 0.95, 95% CI 0.85-1.06) [10]. Results from the large, randomized trials published subsequently are similar. Aspirin did not convincingly reduce the rate of nonfatal presumed ischemic stroke in ASCEND (rate ratio 0.88, 95% CI 0.73-1.06) [13]. In the ARRIVE trial, aspirin did not reduce the rates of fatal or nonfatal stroke (HR 1.12, 95% CI 0.80-1.55) [17]. In the ASPREE trial of patients 70 years of age or older, the rate of fatal or nonfatal ischemic stroke was similar (HR 0.89, 95% CI 0.71-1.11) [15]. Although their point estimates differ, all three trials have relatively wide confidence intervals, and their results are consistent with estimates from the 2016 meta-analysis.
It is possible that the finding of a neutral effect of aspirin's lack of impact on total stroke may represent a small increase in hemorrhagic stroke and a small decrease in ischemic stroke.
Long-term follow-up data from some trials of aspirin in the treatment and prevention of CVD have provided an opportunity to explore possible benefits on cancer incidence and mortality.
Colorectal cancer — Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal carcinogenesis and may influence metastases and related mortality. However, in the absence of another indication for aspirin use, we do not use aspirin to prevent the development of colorectal cancer in the general population. The potential benefit from aspirin in patients at high risk for colorectal cancer is discussed elsewhere. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer".)
●Incidence – Evidence from individual patient data in randomized trials utilized in a meta-analysis with long-term follow-up suggests that aspirin decreases colorectal cancer incidence, but this finding begins to emerge only after 10 years of follow-up [21]. The extent to which participants in either the intervention or control groups used aspirin following the study intervention period is uncertain.
•Short term – The United States Preventive Services Task Force (USPSTF) conducted a meta-analysis of four randomized, controlled trials [22-25] and reported no effect of aspirin on colorectal cancer incidence over a follow-up spanning 0 to 12 years (RR 0.99, 95% CI 0.85-1.15) [26].
Two subsequent randomized trials also failed to demonstrate that aspirin reduced colorectal cancer incidence. In the ASCEND trial, the incidence of gastrointestinal tract cancer was similar in the groups randomized to aspirin and placebo (2 percent in both groups) [13]. Similarly, in the ARRIVE trial, the rate of colon cancer was 0.22 percent in the aspirin group and 0.10 percent in the placebo group at a mean follow-up of five years [17]. (See 'All-cause mortality' above.)
•Long term – Data on longer-term posttreatment follow-up were available for three of the studies in the 2016 USPSTF meta-analysis (British Doctors Study [25], Women's Health Study [27], United Kingdom transient ischaemic attack study [median treatment duration range 4.4 to 10.1 years] [24]). The meta-analyses showed that aspirin use in these studies was associated with a lower long-term risk (10 to 19 years) of colorectal cancer (RR 0.60, 95% CI 0.47-0.76) [26].
●Mortality – Evidence from post hoc analyses of randomized trials suggests that long-term use of aspirin is associated with lower colorectal cancer mortality. Representative examples from the literature include the following:
•In a 2010 meta-analysis of 18-year follow-up from four randomized, controlled trials that included 14,033 participants, aspirin reduced rates of colorectal cancer mortality (HR 0.66, 95% CI 0.51-0.85) [28]. Analyses of pooled individual patient data revealed an absolute reduction of 1.76 percent (0.61 to 2.91 percent) in the 20-year risk of fatal colorectal cancer after at least five years of treatment with low-dose aspirin (75 to 300 mg daily).
•In a 2011 meta-analysis of three randomized trials, aspirin reduced deaths from colorectal cancer (HR 0.60, 95% CI 0.45-0.81) at a follow-up duration of up to 20 years [29].
However, the benefit of aspirin on colorectal cancer mortality is not evident with short-term follow-up. In a 2011 meta-analysis that included 23,535 participants with and without established vascular disease, aspirin did not significantly reduce colorectal cancer mortality during zero to five years of follow-up (HR 0.78, 95% CI 0.39-1.56), although these results were imprecise [29]. Notably, in the 2018 ASPREE trial, over a mean follow-up of five years, colorectal cancer deaths were higher in the aspirin group (0.8 versus 0.5 deaths per 1000 person-years; HR 1.77, 95% CI 1.02-3.06) [16].
A more detailed review of aspirin and other NSAIDs on reducing the risk of colorectal adenomas and cancer, depending on dose and duration of therapy, is discussed elsewhere. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer".)
Other cancers — Evidence provides very limited support for incidence reductions in cancers other than possibly colorectal or for mortality reductions in any cancer. Evidence suggesting reductions in non-colon cancer risk and mortality comes from a restricted set of studies from a single investigative team. The failure of other meta-analyses from a wider selection of studies to confirm these results leaves us skeptical about the possible benefits of aspirin for non-colon cancer outcomes.
●Incidence – The evidence for a beneficial effect of aspirin on cancer incidence is inconsistent [21,30,31]. As an example, a 2019 meta-analysis that included 16 trials and 104,018 participants failed to demonstrate any effect on cancer incidence (RR 0.98, 95% CI 0.92-1.04) at a mean follow-up of 5.5 years [30]. Similarly, the subsequent ASPREE trial of 19,114 community-dwelling older adults did not find a difference in incident cancers between the daily low-dose aspirin and placebo groups (HR 1.04, 95% CI 0.95-1.14) after a median of 4.7 years follow-up [31].
●Cancer-related mortality – The preponderance of evidence from studies in CVD primary prevention populations suggests that aspirin use does not reduce cancer-related mortality.
•Two large meta-analyses of aspirin use for the primary prevention of CVD examined the outcome of cancer-related mortality. Neither identified a clear benefit:
-In a 2019 meta-analysis of 16 trials, aspirin did not reduce cancer-related mortality (RR 0.99, 95% CI 0.87-1.12) [30].
-In a 2015 meta-analysis of 10 CVD primary prevention trials with 103,787 participants, the difference in cancer death with aspirin versus placebo was small and not statistically significant (RR 0.96, 95% CI 0.87-1.06) [32]. Follow-up ranged from 3.7 to 10 years, and aspirin dose ranged from 50 to 650 mg daily.
•In a subsequent large primary prevention trial in older adults, cancer-related mortality was higher in those randomized to low-dose (100 mg daily) aspirin, compared with placebo (6.7 versus 5.1 events per 1000 person-years; HR 1.31, 95% CI 1.10-1.56) [16].
•Some data suggest a small absolute benefit with higher-dose aspirin (≥100 mg daily) given for a duration of five years or greater. As an example, in an earlier meta-analysis, aspirin reduced overall cancer-related mortality, compared with no aspirin (odds ratio [OR] 0.85, 95% CI 0.76-0.96) [21]. When stratified by follow-up duration, only participants followed for >5 years demonstrated a benefit (OR 0.63, 95% CI 0.49-0.82).
Dementia or disability — The primary endpoint of the ASPREE trial was a composite of death, dementia, or persistent physical disability. The rate of this composite endpoint was similar in those receiving or not receiving aspirin at a median of 4.7 years of follow-up (21.5 versus 21.2, respectively) [14].
POTENTIAL RISKS
Bleeding
●Major bleeding – The primary adverse effect of aspirin is major bleeding, typically defined as bleeding from the gastrointestinal tract or other sites that requires hospitalization and/or transfusion. Bleeding most commonly occurs in the gastrointestinal tract and is rarely fatal [33]. Intracranial hemorrhage is the rarest but most serious site of bleeding, with a case fatality rate of 50 percent.
•Overall, aspirin confers a 50 percent increase in the relative risk (RR) of major nonfatal extracranial bleeding over 10 years but only a very small absolute risk increase. As an example, a 2016 meta-analysis of the use of aspirin for primary prevention found that the use of low-dose aspirin (≤100 mg daily or every other day) increased the risk of major gastrointestinal hemorrhage (odds ratio 1.58, 95% CI 1.29-1.95; 1.39 excess events per 1000 person-years) [34].
•In a 2019 meta-analysis of 134,446 participants, which included the ASCEND, ARRIVE, and ASPREE trials, low-dose aspirin use (≤100 mg daily) increased the risk of intracranial hemorrhage (RR 1.37, 95% CI 1.13-1.66; 2 excess intracranial hemorrhages per 1000 persons), compared with placebo, over follow-up periods ranging from two to eight years [35]. The greatest risk was for subdural or extradural hemorrhage (RR 1.53, 95% CI 1.08-2.18).
However, the absolute risk increase in young, healthy individuals is extremely low. This is illustrated in a table that presents the absolute bleeding risks with and without aspirin (table 1).
Patient characteristics that may increase the risk of major bleeding include increasing age, male sex, diabetes, chronic kidney disease, smoking, hypertension, and obesity [34,36]. If a patient has an episode of major bleeding while taking aspirin for primary prevention, the patient and clinician should weigh the risk of recurrent bleeding against the potential benefits of long-term use. Given the very small benefits patients might expect, such individuals may well decide on discontinuation. (See 'Our approach' below.)
Issues related to the primary prevention of gastrointestinal toxicity from nonsteroidal anti-inflammatory drugs (NSAIDs) are discussed in detail elsewhere. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity".)
●Minor bleeding and anemia – Daily low-dose aspirin use may also increase rates of anemia and iron deficiency, particularly in older individuals. In a randomized trial that included 19,114 older individuals (≥65 years for those identified as Black or Hispanic, ≥70 years for White) without known CVD, daily aspirin (100 mg) increased the risk of anemia and iron deficiency, compared with placebo [37]. The risk of anemia, assessed by annual hemoglobin testing, was 51 events per 1000 person-years with aspirin versus 43 events per 1000 person-years with placebo (hazard ratio 1.2, 95% CI 1.1-1.3). The risk of iron deficiency, defined as ferritin <45 ng/mL, was 13 versus 9.8 percent, respectively.
Monitoring for anemia to detect occult bleeding in patients taking daily aspirin is discussed separately. (See "Diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Overview of screening considerations'.)
Aspirin sensitivity — A very small minority of patients are unable to tolerate aspirin because of hypersensitivity, which most often presents with respiratory symptoms, including rhinitis or asthma and, less frequently, urticaria/angioedema (7 to 20 per 10,000 treated) [38-40]. With some forms of aspirin sensitivity, cross-reactions with other NSAIDs can occur. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions".)
In such circumstances, clinicians may consider aspirin desensitization or clopidogrel. (See "Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization", section on 'Desensitization' and "Introduction of aspirin to patients with aspirin hypersensitivity requiring cardiovascular interventions", section on 'Our approach'.)
OUR APPROACH —
The decision to initiate aspirin therapy for primary prevention depends on the patient's estimated risks of CVD, colorectal cancer, and major bleeding, as well as the patient's values and preferences regarding preventing these outcomes.
Risk assessment — Our approach to decision-making regarding aspirin therapy for primary prevention starts by assessing the individual's risk of cardiovascular events, colorectal cancer, and major bleeding with daily aspirin. Although tools exist to estimate the risk of future atherosclerotic cardiovascular disease (ASCVD) and colorectal cancer, none provide a risk-to-benefit calculation that takes all these factors into consideration.
Definitions of risk
●Low risk – We consider a low risk of ASCVD to be a 10-year risk of <5 percent (see "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'Low risk (<5 percent)'). We consider a low risk of colorectal cancer to be a 10-year risk of <2 percent.
●Moderate risk – We consider a moderate risk of ASCVD to be a 10-year risk of ≥5 percent and <20 percent (see "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'Additional risk stratification and management'). We consider a moderate risk of colorectal cancer to be a 10-year risk of ≥2 percent and <5 percent.
●High risk – We consider a high risk of ASCVD to be a 10-year risk of ≥20 percent. These individuals typically have multiple ASCVD risk factors (see "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'High risk (20 percent and higher)'). We consider a high risk of colorectal cancer to be a 20-year risk of ≥5 percent.
Atherosclerotic cardiovascular disease (ASCVD) — We generally combine clinical assessment with results from CVD risk assessment using a risk calculator to estimate the patient's risk of future cardiovascular events. Risk assessment for ASCVD is discussed separately. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults".)
In the United States, we typically use the 2023 Predicting Risk of cardiovascular disease EVENTs (PREVENT) calculator from the American Heart Association (AHA) or the 2018 ASCVD Risk Estimator Plus from the American College of Cardiology (ACC)/AHA [41,42]. Features of specific risk calculators are discussed separately. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)
Colorectal cancer — We also use the patient's family history and prior medical history (eg, number, size, and type of colonic polyps) to assess the individual's risk for colorectal malignancy (see "Screening for colorectal cancer: Strategies in patients at average risk" and "Screening for colorectal cancer in patients with a family history of colorectal cancer or advanced polyp"). The risk of colorectal cancer can be quantified by using risk calculators, such as the National Cancer Institute's Colorectal Cancer Risk Assessment Tool or the QCancer 15-year colorectal risk calculator from the United Kingdom. An elevated risk of colorectal cancer may increase the absolute benefit of aspirin use.
Bleeding — The risk of bleeding often increases in parallel with increased cardiovascular risk, which may limit the net benefit of aspirin therapy in patients at higher risk of ASCVD. Use of concomitant medications known to increase the risk of bleeding while taking aspirin (anticoagulants, nonsteroidal anti-inflammatory drugs) will reduce the net benefit associated with aspirin use.
Ascertain patient values and preferences — In addition to estimating the magnitude of risks and benefits from aspirin therapy, we assess the relative value a patient places on preventing specific outcomes. Individual patients place different values on each outcome, particularly when considering a long-term therapy with low absolute benefit and potential for risk. Some individuals may place greater value on avoiding vascular events or colon cancer. For others, avoiding the small increased risk of intracranial hemorrhage might be most important.
Patient-specific recommendations — After assessing the patient's risk for CVD and cancer and eliciting the patient's preferences and values, we approach decisions regarding aspirin therapy as follows:
Patients ages 70 years and older — In patients 70 years of age and older, we suggest not initiating aspirin for primary prevention. Patients already taking aspirin for primary prevention should rediscuss potential risks and benefits with their clinician upon reaching age 70 because the risks of aspirin typically outweigh the benefits in this group of individuals.
The risk/benefit ratio of aspirin for primary prevention appears not favorable among older adults:
●In the only randomized trial of aspirin for primary prevention that enrolled only patients aged 70 and above, aspirin did not significantly reduce rates of myocardial infarction (MI), stroke, or cardiovascular mortality [15]. Furthermore, the rate of major hemorrhage was higher among those randomized to aspirin therapy than in those randomized to placebo (8.6 events per 1000 person-years versus 6.2; hazard ratio 1.38, 95% CI 1.18-1.62). (See 'Possible benefits' above.)
●The United States Preventive Services Task Force (USPSTF) performed a microsimulation model to assess the magnitude of net benefit of low-dose aspirin use stratified by age and cardiovascular risk [43]. The model found that aspirin resulted in a loss of life years in individuals aged 70 to 79.
This approach is consistent with guidelines from the ACC/AHA [44]. The 2022 USPSTF statement recommends against initiating low-dose aspirin for the primary prevention of CVD and colorectal cancer in adults aged 60 and older [45].
Patients ages 40 to 69 years — For most adults ages 40 to 69, the relative benefits and risks of aspirin therapy for primary prevention are closely balanced. The major potential benefit of long-term aspirin appears to be a reduction in the risk of MI among a small number of individuals. However, the absolute benefit with MI reduction approximates the absolute increase in risk of major bleeding. Aspirin therapy may also slightly reduce colorectal cancer incidence and long-term mortality. (See 'Possible benefits' above and 'Potential risks' above.)
In the USPSTF microsimulation model to assess the magnitude of net benefit of low-dose aspirin use, aspirin initiation provided a modest net benefit in life years in those aged 40 to 59 years with a 10-year risk of ASCVD of 10 percent or higher [43]. In patients ages 60 to 69, the impact of aspirin varied according to age, sex, and cardiovascular risk.
In discussing the decision to take aspirin for primary prevention, we use a summary of the key evidence of aspirin's benefits and risks, as shown in the table (table 1).
●Low risk – For individuals ages 40 to 69 years who are at low risk of ASCVD and colorectal cancer, we suggest not initiating aspirin for primary prevention because the absolute benefits are insufficient to warrant the use of long-term daily aspirin (see 'Definitions of risk' above and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'Low risk (<5 percent)'). As an example, in 1000 patients at age 40 with an estimated 10-year risk of ASCVD of less than 3 percent and a low risk of colorectal cancer (<3 percent), over 980 individuals taking aspirin for 10 years would potentially see no benefit or risk. One could additionally expect five fewer MIs, four more major bleeds, and possibly seven fewer colorectal cancers with aspirin use.
●Moderate to high risk – We individualize decision-making for persons ages 40 to 69 who are at moderate to high risk of ASCVD events and/or colorectal cancer [46] (see 'Definitions of risk' above and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'Additional risk stratification and management'). In these individuals, the risks and benefits of low-dose aspirin are closely balanced, and individual patient values and preferences may inform decision-making about aspirin use. As an example, in 1000 patients at age 60 years and with a risk of CVD events of approximately 15 percent over 10 years and an average risk of colorectal cancer (approximately 5.3 percent over 20 years), aspirin use over a 10-year period would be expected to result in 14 fewer MIs and 11 more major extracranial bleeding events over 10 years follow-up and, possibly, 12 fewer cases of colorectal cancer over a 20-year follow-up. People at the lower range of ASCVD risk (eg, 10-year ASCVD risk between 5 and 10 percent) are unlikely to derive significant benefit from low-dose aspirin therapy.
Those at high risk are most likely to benefit from long-term, daily aspirin (see 'Definitions of risk' above and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'High risk (20 percent and higher)'). However, even in this group, the absolute benefit remains small, and existing data suggest a marginal net benefit (table 1). This group includes individuals whose 10-year risk of an ASCVD event is ≥20 percent, who typically have multiple ASCVD risk factors. It also includes individuals with familial hypercholesterolemia, who are at very high risk for premature CVD. (See "Familial hypercholesterolemia in adults: Overview", section on 'Prognosis' and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults", section on 'High risk (20 percent and higher)'.)
This approach is consistent with guidelines from the 2022 USPSTF, which state that in individuals 40 to 59 years of age who have a 10 percent or greater 10-year risk of ASCVD, the net benefit of low-dose aspirin for primary prevention is small and the decision to initiate aspirin should be individualized [45]. Risk was calculated using the ACC/AHA cardiovascular risk calculator [47,48]. Guidelines from the ACC/AHA recommend consideration of low-dose aspirin (75 to 100 mg orally daily) for the primary prevention of CVD among adults 40 to 70 years of age who are at higher risk of CVD but not at increased risk of bleeding [44].
Dosing — For individuals who decide to initiate aspirin therapy for primary prevention, we use a dose of 75 to 100 mg daily. Available evidence suggests that, for primary prevention, aspirin doses of 75 to 100 mg daily are sufficient to achieve the benefits of cardiovascular risk reduction [49]. The optimal dose of aspirin for reducing the risk of colorectal cancer is unclear. Doses of ≤100 mg per day minimize the risk of bleeding [34,50].
The potential relationship between dose, body weight, and outcomes is discussed separately. (See "Nonresponse and resistance to aspirin", section on 'Body weight'.)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Aspirin to prevent heart attacks and cancer (The Basics)")
●Beyond the Basics topic (see "Patient education: Aspirin in the primary prevention of cardiovascular disease and cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Possible benefits – Although aspirin produces important reductions in cardiovascular disease (CVD) mortality and morbidity among survivors of a wide range of atherosclerotic cardiovascular events (secondary prevention), the benefits and harms are closely balanced in apparently healthy people (primary prevention). In patients without prior CVD events, aspirin decreases the risk of nonfatal myocardial infarction (MI) but increases the risk of major bleeding. Aspirin possibly reduces the risk of colorectal cancer over long-term follow-up (with >10 years of treatment). (See 'Possible benefits' above and 'Colorectal cancer' above and 'Bleeding' above.)
●Risk assessment – Our individualized approach to decision-making regarding aspirin therapy for primary prevention starts by assessing the individual's risk of cardiovascular events, colorectal cancer, and major bleeding with daily aspirin. Although many tools estimate the risk of future atherosclerotic cardiovascular disease (ASCVD), none provide a risk-to-benefit calculation that takes all these factors into consideration. (See 'Risk assessment' above.)
●Eliciting patient values and preferences – Following an assessment of the patient-specific risks and benefits of aspirin therapy for primary prevention, we elicit the patient's values and preferences regarding aspirin therapy. This includes the patient's attitude toward taking a long-term daily medication and the relative value placed on preventing specific outcomes, including the immediate increase in the risk of bleeding versus the delayed potential benefit on CVD and cancer. (See 'Ascertain patient values and preferences' above.)
●No aspirin for most patients – In persons ages 70 years or older and those ages 40 to 69 who are at low risk of ASCVD events or colorectal cancer, we suggest not initiating aspirin for primary prevention (Grade 2C). "Low risk" includes a 10-year risk of ASCVD of <5 percent and a 20-year risk of colorectal cancer of <5 percent. For these patients, the balance of risks and benefits favors not starting aspirin. (See 'Definitions of risk' above and 'Patient-specific recommendations' above.)
●Individualized decision-making in those at moderate to high risk – We individualize the decision regarding aspirin for primary prevention in individuals ages 40 to 69 years who are at moderate and high risk of CVD and cancer. "Moderate to high risk" includes those with a 10-year risk of ASCVD of ≥5 percent and a 20-year risk of colorectal cancer of ≥5 percent. (See 'Definitions of risk' above and 'Patient-specific recommendations' above.)
For most of these patients, the benefits and harms of aspirin therapy for primary prevention are closely balanced. In patients at higher ASCVD and/or colon cancer risk who are not averse to using medication, more worried about preventing MI, less worried about bleeding, and optimistic about a possible reduction in colon cancer incidence, low-dose daily aspirin is a reasonable choice. The table provides a succinct summary of the key evidence that may aid the discussion (table 1). (See 'Patients ages 40 to 69 years' above.)
●Dosing – For individuals who decide to initiate aspirin therapy for primary prevention, we use a dose of 75 to 100 mg daily, which is optimal for ASCVD risk reduction and minimizing the risks of bleeding. (See 'Dosing' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Charles H Hennekens, MD, FACPM, FACC, who contributed to earlier versions of this topic review.
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