By Robert M. Zimbroff, MD; Gina Ayers, PharmD, BCPS, BCGP; and Kenneth Koncilja, MD
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No. Recent evidence shows that the potential risks of aspirin use for the primary prevention of cardiovascular disease usually outweigh its benefits for patients age 70 and older.
An updated draft of the United States Preventive Services Task Force (USPSTF) recommendations regarding aspirin use were released for public comment in October 2021. These guidelines have a grade C recommendation against initiating low-dose aspirin for the primary prevention of cardiovascular disease in patients ages 40 to 59 with a 10% or greater 10-year risk of cardiovascular disease. Furthermore, the guidelines offer a grade D recommendation against initiating low-dose aspirin for the primary prevention of cardiovascular disease in adults age 60 and older. This guidance is a change from the organization’s 2016 recommendation, which was equivocal on adults ages 60 to 69 and avoided a recommendation for adults age 70 and older, citing insufficient evidence.
In 2018, results from three large double-blind, randomized, placebo-controlled trials offered insight into how to approach aspirin use for primary prevention in older adults. These trials — Aspirin in Reducing Events in the Elderly (ASPREE), Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE), and Aspirin for Primary Prevention in Persons with Diabetes Mellitus (ASCEND) —provide substantial data regarding when to consider prescribing or de-prescribing aspirin for older patients.
The ASPREE trial
This trial enrolled 19,114 community-dwelling older adults (≥70 years old, or ≥65 years old for Black and Hispanic patients without evidence of cardiovascular disease. During a median follow-up of 4.7 years, researchers found that 100 mg/day of aspirin provided no benefit in preventing nonfatal cardiovascular events or death or in increasing disability-free survival. Aspirin use increased the risk of clinically significant, nonfatal major hemorrhage, defined as a composite measure of intracranial and upper or lower gastrointestinal bleeding that prolonged hospitalization or required transfusion, hospitalization, or surgical intervention. Unexpectedly, the aspirin cohort had higher all-cause mortality, which was attributed to increased cancer-related mortality. Mortality from major bleeding events, including hemorrhage or hemorrhagic stroke, was no different between groups.
The ARRIVE trial
This study enrolled 12,546 patients age 55 and older (men) and age 60 and older (women) with moderate cardiovascular disease risk assessed by the presence of factors such as current tobacco use, low levels of high-density lipoprotein cholesterol, elevated systolic blood pressure (>140 mm Hg), prescriptions for antihypertensive medications, or a positive family history of cardiovascular disease. The trial was focused on primary prevention, so investigators excluded participants with prior cardiovascular events or interventions (e.g., stenting, angioplasty, bypass surgery). Patients with diabetes were also excluded. The intent-to-treat analysis showed no significant benefit for aspirin use of 100 mg/day at 5-year follow-up. A subgroup analysis showed no benefit for patients age 65 and older. As in earlier studies, the aspirin-receiving cohort had an increased risk of gastrointestinal bleeding.
The ASCEND trial
This trial enrolled 15,480 participants with diabetes but without known cardiovascular disease; nearly one-quarter of participants enrolled were at least 70 years of age. Although 100 mg/day of aspirin successfully reduced first vascular events, a subgroup analysis revealed no benefit for patients age 70 and older. Aspirin use was associated with a higher risk of major bleeding events, defined as bleeding that prolonged hospitalization; required transfusion, hospitalization, surgical intervention, or intensive care unit admittance; or caused death. This risk was significant for patients age 60 and older but was not significant for younger patients.
Reaction of medical societies
In light of these findings, the American College of Cardiology (ACC) updated its practice guidelines in 2019 to state that low-dose aspirin should not be administered on a routine basis for the primary prevention of atherosclerotic cardiovascular disease in adults over age 70. In 2021, the American Diabetes Association (ADA) similarly stated that aspirin use appears to carry more risks than benefits and thus is not recommended in these patients.
Complementary interventions aimed at reducing the risk of cardiovascular events — statins for hyperlipidemia, improved antihypertensive medications, and aggressive anti-smoking campaigns — may further reduce the utility of aspirin for primary prevention. Nevertheless, data from the National Health and Nutrition Examination Survey (2011-2018) showed that aspirin use for primary prevention significantly increased as patients age, from 24% in ages 50 to 54 to 45.3% in patients age 75 and older.
Utility of aspirin for the prevention of colorectal cancer
In addition, there is increasingly clear evidence to support the discontinuation of aspirin for colorectal cancer prevention in older adults. The USPSTF previously made a grade B recommendation to support the use of low-dose aspirin in adults ages 50 to 59; this decision was based, in part, on evidence showing a reduced incidence of colorectal cancer after 5 to 10 years of use. A more recent pooled analysis of data on 94,540 participants age 70 and older from both the longitudinal Nurses’ Health Study and the Health Professionals Follow-up Study found that aspirin use was associated with a lower incidence of colorectal cancer after age 70 for patients who initiated aspirin before age 70 with at least 5 years of use Initiating aspirin after age 70 was not associated with a reduced risk of colorectal cancer. The ASPREE investigators reported increased cancer-associated mortality risk in the aspirin-use cohort (including higher colorectal cancer mortality); however, they noted that this result was unexpected in the context of other well-designed aspirin trials and should be interpreted cautiously.
The bottom line
Proposed updates put the USPSTF’s recommendations in line with those of the ACC and ADA regarding aspirin use for primary prevention in adults age 60 and older. Our clinical recommendation reflects the revised USPSTF guidelines: The risks of aspirin use outweigh its benefits in older adults. Providers, in conjunction with patients, should de-prescribe aspirin as able.
This article, which has been edited for length, originally appeared in the Cleveland Clinic Journal of Medicine.