Think You Need a Statin? AHA’s Risk Calculator May Disagree

Millions of US adults would no longer need to take a statin for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) if their eligibility were based on the new PREVENT risk calculator instead of the older pooled cohort equations (PCEs), a new analysis shows.

Replacing the PCEs with the American Heart Association’s Predicting Risk of CVD Events (PREVENT) tool, more than 17 million adults previously recommended statins for primary prevention would no longer be eligible for the lipid-lowering therapy. This includes “4.1 million adults currently taking statins,” write lead researcher Timothy Anderson, MD (University of Pittsburgh, PA), and colleagues online in JAMA Internal Medicine.  

Those no longer deemed to have a high enough risk to warrant a statin could stop treatment, although this may end up sowing some confusion, say investigators, especially since many might need them again as they age.

Preventive cardiologist Sadiya Khan, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), who led the development and validation of the AHA’s PREVENT calculator, said that when they tested it alongside the PCEs, they, too, found that the older tool overestimated ASCVD risk by a factor of two, just as this new research shows. PREVENT is a more contemporary risk calculator, she added, developed from 25 datasets that included more than 3.3 million people and validated in 21 additional datasets with another 3.3 million patients.

“A person’s risk doesn't change based on the model you use, but a more accurate model allows you to better estimate risk,” Khan told TCTMD. “That’s what we’re getting now [with PREVENT]. Of course, it’s a difficult thing [for patients] to then say, ‘Well, yesterday we were using the pooled cohort equations and maybe in the future we will use the new model.’”

She emphasized, however, that patients and prescribing physicians should not use these new findings to stop or start therapies, such as statins.

“I think the concern is that the translation or the messaging from the data may go beyond what it's showing,” said Khan. “That fewer people should be on statins, I think that’s been the implication of the findings, but it presumes that the guidelines would recommend the same risk threshold [for initiating statins with PREVENT]. I don't think that's necessarily true. I don't think we know yet. I would say until there are new guidelines, the most important message for both clinicians and patients is that these are observational, cross-sectional data and they cannot inform practice.”

Preventive cardiologist Nilay S. Shah, MD (Northwestern University Feinberg School of Medicine), who wasn’t involved in developing PREVENT, said he hasn’t yet encountered any patients in practice wondering if they could now come off statins, but it may yet happen.

As for the potential switch from the PCEs to PREVENT, this study suggests that patients are almost exclusively moved from a higher-risk category to a lower one, with very few people going the other direction, said Shah.

“That would imply that there’s a lot more room for shared decision-making,” he told TCTMD. “If people are moved from a high-risk to a more intermediate-risk category, our foundational principles of prevention would guide us to say that this is an opportunity for everybody to really understand an individual’s specific risk factors and what might modify their absolute risk.”

PREVENT Equations Over PCEs

The 2018 guidelines for managing cholesterol and 2019 guidelines for primary prevention currently use the PCEs to help stratify patient risk and to guide treatment decisions. The PREVENT calculator, developed from a larger, more diverse population, is an update to the PCEs, which were first released in 2013 to estimate the 10-year risk of ASCVD. The PCEs have been criticized in the past for overestimating patient risk and being less accurate in some groups, such as Asian and Hispanic adults, because they were underrepresented in the older datasets used to develop the calculator. 

PREVENT captures a spectrum of cardiovascular, kidney, and metabolic risk by factoring in renal function and statin use, as well other optional variables such as hemoglobin A1c, urinary albumin-to-creatinine ratio, and the social deprivation index. It provides estimates of the 10- and 30-year risks of MI, stroke, and heart failure in people as young as 30 years old.

For this study, Anderson and colleagues used data from the National Health and Nutrition Examination Survey to compare how the PCEs and PREVENT equations affected national estimates of 10-year ASCVD risk and primary prevention statin therapy in the United States. Eligibility for statin therapy was based on the 2019 primary prevention guidelines that recommend statins for three groups: those with diabetes, those with LDL cholesterol levels > 190 mg/dL, and those with an intermediate or greater 10-year risk of ASCVD (≥ 7.5%).

Among 3,785 adults (mean age 55.7 years; 52.5% female), the mean estimated 10-year risk of ASCVD was 8.0% using the PCEs and 4.3% using the PREVENT equations. In all age groups, males and females, and racial subgroups, the estimated risk of ASVCD was higher using the PCEs. The differences in risk were highest for Black adults and for older patients.

If the PREVENT equations were used instead of the PCEs, 40.8% of US adults would be reclassified by shifting downwards to a lower-risk category. For the 29.3 million adults considered intermediate risk based on the PCEs, 25.6% would be shifted into the low-risk category and 46.2% into the borderline-risk category (5% to < 7.5%). Among the 9.8 million high-risk patients based on the PCEs, PREVENT would reclassify 94.0% into the intermediate-risk category.

No matter what model you use, what threshold you use, we are undertreating primary prevention patients. Sadiya Khan, MD

The number of adults meeting the criteria for primary prevention statin therapy would thus be reduced from 45.4 million to 28.3 million adults if guidelines adopted PREVENT over the PCEs. The findings were consistent across multiple subpopulations and levels of risk. Overall, just 44.1% of those sampled and deemed eligible for statin therapy using the new PREVENT equations—which would represent more than 15 million US adults—were currently taking the drugs.

PREVENT Is More Accurate

Shah said he wasn’t too surprised by the findings given that it’s been shown previously the PCEs overestimate risk for many populations. Still, it’s notable that there are other groups, such as certain Asian populations, where the PCEs underestimated ASCVD risk.

In general, patients need help understanding their risk of ASCVD and the calculators are just the beginning, he added.

“The PREVENT equations are a place to start, but there are facts that are not included in the PREVENT model or any risk model that we have to take into account,” he said. “As a physician, my job is not to make a value judgment for the patient, but to help patients assess and judge and weigh [the evidence]. When a patient falls into the intermediate-risk category, it's really my priority to help them make an informed decision.”

As for the potential millions of US adults who could be downgraded and thus wouldn’t be eligible for statins with PREVENT, Shah sees this is an opening for doctors to help people make the right choice based on their individual risk factors and values.

Like Shah, Khan said that the decision to start a statin for primary prevention remains quite nuanced, with risk estimation using any calculator just a starting point for the physician-patient discussion.

“With most of patients, I'm assessing overall risk and talking about the different ways we can reduce their risk for heart disease,” she said. “Statin therapy is one way, and then there's lifestyle, dietary interventions, physical activity—we talk about all of them together.” With statins, she added, what’s pertinent is understanding how the LDL cholesterol-lowering therapy addresses the individual’s risk factors.

In their paper, Anderson and colleagues suggest that the next guidelines “may even consider moving away from precise treatment thresholds toward recommendations that encourage risk communication and shared decision-making.”

Khan added that the study also highlights the well-known implementation gap, with more than half of eligible patients not treated with statins. “No matter what model you use, what threshold you use, we are undertreating primary prevention patients,” she said.