Pooled Cohort Equations Outperform PREVENT in Predicting ASCVD Risk Without Statins

The Predicting Risk of Cardiovascular Disease Events (PREVENT) model underestimates risk of atherosclerotic cardiovascular disease (ASCVD) in patients not treated with statins compared to the Pooled Cohort Equation (PCE) model, according to recent research.1

The PCE model, derived in 2013, is endorsed by current national guidelines for estimating 10-year rates of ASCVD events. The equations were based on cohort studies including predominantly Black and White participants. In modern cardiology, concerns have been raised regarding the generalizability of the PCE model in a more diverse patient population.2

To this end, the American Heart Association introduced the PREVENT model in 2023, an updated assessment model developed for a more contemporary patient group. PREVENT also removes race as a predictor, replacing it with the Social Deprivation Index, which is a zip code-based proxy for social determinants of health. Because it was constructed with a cardiovascular-kidney-metabolic health framework, PREVENT also accounts for kidney function and body mass index (BMI).1

Despite the progress that PREVENT represents, its effectiveness in a large, unselected population has not been comprehensively evaluated. Prior trials have not taken the presence of prior statin treatment into account – given that risk prediction models are designed to estimate baseline cardiovascular risk without treatment, a trial was proposed to compare PREVENT and PCE in evaluating untreated individuals.1

“A strength of this analysis is its ability to account for statin exposure using detailed pharmacy records from an integrated health care system,” Ming-Sum Lee, MD, PhD, department of cardiology, Kaiser Permanente Los Angeles Medicine Center, and colleagues wrote. “By comparing observed ASCVD incidence with estimated risk in statin-treated and untreated subgroups, this study provides an assessment of the validity of 2 major cardiovascular risk prediction models, informing their optimal use in contemporary, diverse populations.”1

Investigators included 193,885 participants, all Kaiser Permanente Southern California (KPSC) health plan enrollees and with a mean age of 55 years. Participants had low-density lipoprotein cholesterol (LDL-C) levels between 70 and 189 mg/dL. Patients were excluded if they had a history of dialysis, hospice care, a baseline history of ASCVD such as myocardial infarction, ischemic stroke, peripheral artery disease, or diabetes.1

Patients were followed up with from the index date – noted as the first qualifying lipid panel measurement – until first occurrence of an ASCVD event, death, disenrollment from the health plan, or the study end date. The primary outcome was incident ASCVD, defined as acute myocardial infarction, fatal or nonfatal stroke, or coronary heart disease death.1

Investigators used both PREVENT and PCE to calculate the 10-year estimated ASCVD risk. Patients were then stratified into 4 risk groups based on guideline-recommended thresholds for statin initiation and intensification: <5%, 5 to <7.5%, 7.5 to <10%, and ≥10%. Statin exposure was determined via outpatient pharmacy dispensing records, and patients were considered exposed during the trial if they obtained at least 1 dispensing of statin between index date and the end of follow-up.1

Over the course of follow-up, there were 6528 incident ASCVD events. Higher event-free survival was observed in patients exposed to statin, with the highest event free-survival observed among those exposed to statin for >80% of the follow-up period. Observed and estimated 10-year incidence rates were compared with baseline risk categories.1

The overall population, regardless of statin exposure, saw a lower ASCVD risk than estimated by PCE: 3.6% for the 5 to <7.5% cohort, 4.5% for the 7.5 to <10% cohort, and 8% for the ≥10% cohort. Observed risk was more closely aligned with PREVENT’s estimated risk: 5.2% for the 5 to <7.5% cohort, 8.1% for the 7.5 to <10% cohort, and 11.6% for the ≥10% cohort. However, risk in patients without statin exposure during follow-up was underestimated by PREVENT, while PCE more closely approximated the observed risk in participants.1

“Risk estimates from PREVENT tend to be lower than those from the PCE and lower than the observed risk in patients not treated with statins,” Lee and colleagues wrote. “When used to guide statin initiation decisions, relying on PREVENT alone to estimate what a patient’s 10-year risk would be without statin therapy may lead to undertreatment.”1

References

1. Lee M, Onwuzurike J, Wu Y, Palmer-Toy DE, An J, Chen W. PREVENT and PCE Models for Estimating ASCVD Risk Stratified by Statin Exposure. JAMA Netw Open. 2025;8(9):e2532164. doi:10.1001/jamanetworkopen.2025.32164

2. Anderson TS, Wilson LM, Sussman JB. Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations. JAMA Intern Med. 2024;184(8):963-970. doi:10.1001/jamainternmed.2024.1302