Low-Dose Aspirin May be Widely Overused for CVD Prevention Based on PREVENT Estimates

A new analysis published in JAMA Internal Medicine reveals that use of the American Heart Association’s new PREVENT equations to guide the use of low-dose aspirin (LDA) for primary prevention of cardiovascular disease (CVD) eliminates eligibility for 86% of adults previously qualified, a population considered candidates based on use of the older Pooled Cohort Equations (PCE).

This finding translates to approximately 4.2 million US adults aged 40 to 59 years now moving off the eligibility roster, underscoring the immediate need for a PREVENT-specific risk threshold to safely guide therapy, according to study authors.

Why the Drastic Drop in Eligibility?

The significant reduction stems from the improved calibration of the PREVENT equations. PCEs, developed years ago, commonly overestimated atherosclerotic CVD (ASCVD) risk in contemporary populations.2 PREVENT corrects this bias, providing better-calibrated, and therefore lower, 10-year ASCVD risk estimates.²

The USPSTF currently gives a grade C recommendation for considering LDA in primary prevention for non-high-bleeding-risk adults aged 40 to 59 years with a 10-year ASCVD risk of 10% or greater.³ This established threshold attempts to ensure a positive net clinical benefit. First author Ahmed Sayed, MBBS, Rochester General Hospital, Rochester, New York, and colleagues conducted this study to quantify the real-world impact of the new calculator on this critical threshold.

The Data

Using 2015 to 2020 data from the National Health and Nutrition Examination Survey, Sayed et al analyzed 59.4 million US adults aged 40-59 (mean age 49.1, 51.9% women) without established ASCVD or high-bleeding-risk factors (such as eGFR less than 30 mL/min/1.73 m² or history of heart failure). The researchers calculated 10-year ASCVD risk using both PCEs and PREVENT.

The results confirm the wide difference in estimated risk:

PCE eligibility: Using the 10% threshold, 8.3% of the cohort (representing 4.9 million adults) qualified for LDA.

PREVENT eligibility: Applying the identical 10% threshold, only 1.2% of the cohort (representing just 700,000 adults) qualified.

This means that nearly 9 in 10 (85.9%; 95% CI, 81.5%-89.4%) of adults identified as eligible for LDA by PCE estimates are not eligible by PREVENT.

LDA Overuse and Clinical Action

The researchers emphasize that the findings also provide a clear directive for addressing existing aspirin overuse. The study showed that among the 7.6 million adults who reported taking aspirin for primary prevention, an alarming 96.9% (95% CI, 95.1%-98.1%) did not meet the 10% risk criteria when calculated by PREVENT.

This high percentage of non-qualifying users, coupled with the new lower risk scores from PREVENT, reinforces that “there is considerable room to discontinue aspirin in patients who are unlikely to benefit,” the authors wrote.

Key Implications for Primary Care

• Continuing to use the 10% threshold with PREVENT will dramatically under-identify appropriate candidates, as this threshold was calibrated for the higher PCE scores.
• The majority of adults currently on LDA for primary prevention may not be receiving a net clinical benefit and should be reviewed for discontinuation using the new, lower PREVENT scores.

The authors stress the necessity of a dedicated modeling study to determine the PREVENT-specific risk threshold that accurately reflects a positive net benefit for aspirin. Until that new guidance is established, clinicians must use caution and recognize that PREVENT fundamentally changes the primary prevention landscape.

Among the study's limitations the authors acknowledge the reliance on self-reported data and its 2015-2020 timeframe, but suggest they do not diminish the central finding: PREVENT has fundamentally changed the risk scores, and the 10% eligibility line must be redrawn. Clinicians must be prepared to de-escalate aspirin use aggressively in low-risk patients while awaiting new guidelines tailored to the superior PREVENT equations, they concluded.

References

1. Sayed A, Peterson ED, Khera A, Virani SS, Navar AM. Using the PREVENT equations to guide aspirin use for primary prevention of cardiovascular disease. Research letter. JAMA Intern Med. Published online September 29, 2025. Accessed October 13, 2025. doi: 10.1001/jamainternmed.2025.5049

2. Khan SS, Matsushita K, Sang Y, et al. Development and validation of the American Heart Association’s PREVENT equations. Circulation. 2024;149(6): 430-449. doi:10.1161/CIRCULATIONAHA.123.067626

3. Davidson KW, Barry MJ, Mangione CM, et al. Aspirin use to prevent cardiovascular disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577-1584. doi:10.1001/jama.2022.4983