PREVENT Equations Could Result in 100,000 CVD Events by Reducing Statin, Antihypertensive Prescribing

Arjun Manrai, PhD
Credit: Harvard Medical School

A new study is cautioning cardiologists and other care providers about pitfalls within the American Heart Association (AHA)’s recently introduced Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations for predicting long-term cardiovascular risk and determining treatment eligibility.

Results of the study suggest use of the PREVENT equations could result in underprescription of statins and antihypertensive agents, with the downstream effect being an additional 107,000 atherosclerotic cardiovascular disease (ASCVD) events over 10 years relative to current pooled cohort equations (PCE).

“With no change to current risk-based treatment thresholds, widespread adoption of the PREVENT equations for ASCVD risk could reduce eligibility for statin and antihypertensive therapies among an estimated 15.8 million US adults and thereby increase the rate of major adverse cardiovascular events,” wrote investigators.¹ “Although PREVENT advances the important goal of more accurate and precise cardiovascular risk prediction, the magnitude of these projected changes warrants careful reconsideration of current treatment thresholds using decision-analytic or cost-effectiveness frameworks”

The AHA introduced the Predicting Risk of Cardiovascular Disease Events (PREVENT) risk calculator at their 2023 annual meeting with the aim of better incorporating cardiovascular-kidney-metabolic syndrome in cardiovascular disease risk prevention. The AHA designed its risk equation to assess cardiovascular risk in people from ages 30 to 79 years and to predict risk for heart attack, stroke, and/or heart failure over the next 10 years and 30 years. A key difference from the PCE established in 2013 is the incorporation of kidney function and HbA1c into the risk equation.^1,2

At the time of release, the cardiology community lauded the addition of a new risk equation promising improved stratification. However, the interest for many soon shifted to the potential clinical implications of using this new system, which has already been evidenced in published work since the release.1,²

A previous study from June 2024 conducted by investigators at the University of Pittsburgh concluded the use of the PREVENT equations rather than PCEs could reduce the number of adults meeting criteria for primary prevention statin therapy from 45.4 million (95% CI, 40.3 to 50.4) to 28.3 million (95% CI, 25.2 to 31.4). Further expanding on this finding, investigators pointed out that discontinuing use of PCEs in favor of PREVENT equations could result in 17.3 million (95% CI, 14.8 to 19.7) adults recommended statins to no longer be recommended statins, including 4.1 million (95% CI, 2.8 to 5.5) adults who are currently taking statins.²

In the current study, a team of investigators led by Arjun Manrai, PhD, assistant professor of Biomedical Informatics at Harvard Medical School, sought to further the community’s understanding of how use of the PREVENT equation might influence eligibility for statin and antihypertensive therapy relative to PCE using data from the National Health and Nutrition Examination Surveys (NHANES). Using survey data from 2011 to March 2020, investigators identified information from a nationally representative sample of 7765 US adults aged 30 to 79 years for inclusion in the study.¹

The primary outcomes of interest for the investigators’ analyses were differences in predicted 10-year ASCVD risk, ACC and AHA risk categorization, eligibility for statin or antihypertensive therapy, and projected occurrences of myocardial infarction or stroke.¹

Upon analysis, results suggested use of PREVENT would reclassify more than half of US adults to lower ACC and AHA risk categories, with less than 1% of adults being recategorized into higher risk categories (0.41%; 95% CI, 0.25 to 0.62). When using PREVENT, results indicated the number of adults receiving or recommended preventive statin therapy would decrease by a projected 14.3 million (95% CI, 12.6 million to 15.9 million). Similarly, the number of adults receiving or recommended preventive antihypertensive therapy would decrease by a projected 2.62 million (95% CI, 2.02 million to 3.21 million).¹

Investigators highlighted these decreases in treatment eligibility could result in an additional 107,000 ASCVD events occurring over a 10-year period. Investigators also pointed out this projected increase was more apparent among men than women (0.077% vs 0.039%), but similar among Black and White adults (0.062% vs 0.065%).¹

In an editorial, Jelani Grant, MD, Chiadi Ndumele, MD, PhD, and Seth Martin MD, MHS, celebrate the efforts of the study’s investigators for what they describe as a “meticulous, well-designed, and well-written study”. In the editorial, the group points out there is no perfect risk estimation equation and this data should be viewed as formative for highlighting future research topics related to use of the PREVENT-ASCVD risk score.³

“The takeaway should not be that a large proportion of US adults receiving primary prevention will be ineligible for preventive therapies using PREVENT-ASCVD. Rather, the key message is that the establishment of optimal PREVENT-ASCVD risk thresholds for guiding therapy is critical in the development of future guidelines,” wrote the trio. “PREVENT-ASCVD offers a pathway to more accurate and inclusive risk prediction, can be used to motivate sustained lifestyle changes, and can help focus statin and antihypertensive therapy on those most likely to benefit,” the trio wrote.³ “In the meantime, as a medical community, we can redouble our efforts to implement existing cardiovascular prevention guidelines and thereby address the leading cause of death in the US and globally.”

References:

1. Diao JA, Shi I, Murthy VL, et al. Projected Changes in Statin and Antihypertensive Therapy Eligibility With the AHA PREVENT Cardiovascular Risk Equations. JAMA. Published online July 29, 2024. doi:10.1001/jama.2024.12537
2. Anderson TS, Wilson LM, Sussman JB. Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations. JAMA Intern Med. Published online June 10, 2024. doi:10.1001/jamainternmed.2024.1302
3. Grant JK, Ndumele CE, Martin SS. The Evolving Landscape of Cardiovascular Risk Assessment. JAMA. Published online July 29, 2024. doi:10.1001/jama.2024.13247