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Statin Candidate Pool Shrinks if PREVENT Risk Calculator Is Put to Current Practice

— Fewer people using primary prevention medications expected to result in more CVD

July 29, 2024    Last Updated July 30, 2024

The rules for statin and blood pressure (BP) medication initiation may need to be rewritten if a new and improved cardiovascular risk prediction tool is broadly implemented, research suggested.

Use of the PREVENT equations would reclassify 53% of U.S. adults to lower atherosclerotic cardiovascular disease (ASCVD) risk categories -- and just 0.41% to higher risk categories -- as currently defined by the American College of Cardiology (ACC) and American Heart Association (AHA).

These risk estimates, if applied to existing treatment criteria, would bring the number of eligible statin users down from 81.8 million to 67.5 million, and candidates for antihypertensive therapy down from 75.3 million to 72.7 million, according to nationally representative projections by Arjun Manrai, PhD, of Harvard Medical School, and colleagues.

The expected result: 107,000 additional instances of myocardial infarction (MI) or stroke over 10 years, the authors reported in JAMA.

"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," Manrai's group concluded.

Introduced last year, the AHA's PREVENT risk calculator estimates heart attack, stroke, and heart failure risk over 10 or 30 years for adults as young as 30.

PREVENT reportedly gives more accurate and precise risk estimates across the entire population and within demographic subgroups. This is partly because the equations take out race from the calculation and also because they were developed in newer derivation populations compared with the older pooled cohort equations (PCEs), dating back to 2013, that have been known to underestimate risk for some racial and ethnic groups.

Rather than drawing the conclusion from the present findings that "a large proportion of U.S. adults receiving primary prevention will be ineligible for preventive therapies using PREVENT-ASCVD ... the key message is that the establishment of optimal PREVENT-ASCVD risk thresholds for guiding therapy is critical in the development of future guidelines," stressed Seth Martin, MD, MHS, of Johns Hopkins Hospital in Baltimore, and two colleagues in an accompanying editorial.

The ACC and AHA have not endorsed replacing the PCEs with PREVENT in their guidelines. Regardless of the risk calculator used, an ASCVD 10-year risk of 7.5% or above is the current risk minimum for primary prevention statin therapy.

Manrai and co-authors pointed out potential harms from overtreating low-risk populations, such as an increased diabetes risk with statins, and the potential for orthostatic hypotension, organ ischemia, or sexual dysfunction with pharmacologic treatment of high BP.

Thus, the editorialists suggested keeping the risk thresholds for 10-year ASCVD based on the PCEs and in use by current AHA/ACC treatment guidelines.

JAMA Cardiology associate editor Sadiya Khan, MD, MSc, and previous AHA president Donald Lloyd-Jones, MD, ScM, both from Northwestern University Feinberg School of Medicine, Chicago agreed in a viewpoint article: "Until new guidelines are available that include a thorough assessment of the threshold for treatment based on the best contemporary evidence for benefits and harms of statin use, the evidence supports continuing statin use in those patients in whom statin initiation was based on older risk prediction models, with the essential caveat that patients and clinicians should continue to engage in shared decision-making when discussing CVD [cardiovascular disease] risk and therapeutics for primary prevention."

"Given the benefits of statins down to a low level of risk and the low rates of harms, a net benefit threshold as low as a predicted ASCVD risk of 3% to 5% may now be reasonable based on the mean event rates in Cholesterol Treatment Trialists and JUPITER," the duo nevertheless suggested.

For their study, Manrai and colleagues relied on National Health and Nutrition Examination Surveys from 2011 to 2020 to create a nationally representative study sample of 7,765 adults age 30-79.

The PCE-based treatment modeling was done on people age 40-79 with no history of MI or stroke, while the PREVENT modeling included those 30-79 without prior MI, stroke, or heart failure.

The total sample had a median age of 53 years, with 51.3% women.

As expected, PREVENT risk scores were typically lower: mean 10-year ASCVD risk was 9.0% with PCEs and 4.6% with PREVENT, according to the investigators.

They acknowledged that the treatment modeling they did only assessed ACC/AHA class I recommendations and did not account for treatment decisions based on shared decision-making with patients and risk-enhancing factors. Another caveat of the study was that the prepandemic data may not be reflective of the contemporary population, they said.

"It must also be acknowledged that there is no perfect risk estimation equation," Martin's group noted with the suggestion that the PREVENT equations are here to stay.

"Getting comfortable with the PREVENT equations now can help prepare clinicians for an easier transition when these equations are formally adopted into AHA/ACC treatment guidelines," according to the editorialists.

 

Disclosures

The study was supported by an award from the National Heart, Lung, and Blood Institute (NHLBI).

Manrai disclosed receiving NIH/NHLBI grants. Study coauthors reported various ties to industry.

Martin reported receiving equity from Corrie Health; nonfinancial support from Apple; grants from Google; serving on the Care Access advisory board; personal fees for consulting from Amgen, AstraZeneca, Bristol Myers Squibb, Chroma, Kaneka, NewAmsterdam Pharma, Novartis, Novo Nordisk, Premier, Sanofi, and 89bio; and research support from the AHA, Patient-Centered Outcomes Research Institute, NIH, the David and June Trone Family Foundation, the Pollin Digital Innovation Fund, Sandra and Larry Small, Google, and Merck.

Khan reported receiving grants from the AHA and NHLBI.

Lloyd-Jones reported serving as an unpaid fiduciary member of the board of directors of the AHA.

Primary Source

JAMA

Source Reference: Diao JA, et al "Projected changes in statin and antihypertensive therapy eligibility with the AHA PREVENT cardiovascular risk equations" JAMA 2024; DOI: 10.1001/jama.2024.12537.

Secondary Source

JAMA

Source Reference: Grant JK, et al "The evolving landscape of cardiovascular risk assessment" JAMA 2024; DOI: 10.1001/jama.2024.13247.

Additional Source

JAMA

Source Reference: Khan SS, Lloyd-Jones DM "Statins for primary prevention of cardiovascular disease -- with PREVENT, what's a clinician to do?" JAMA 2024; DOI: 10.1001/jama.2024.13887.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine.