Millions fewer people may need statins, a new study suggests. But guidelines have yet to agree

It’s a familiar scene for patients during a routine primary care visit. The doctor scans blood test results, notes high cholesterol flagged by a standard calculator to assess risk of heart attack or stroke, then decides — and ideally discusses — whether to recommend taking a statin to cut the risk over time.

That conversation may happen less often if changes in the risk model presented by the American Heart Association in November translate into new guidelines for prescribing statins. Those guidelines haven’t been recalibrated yet, but a new analysis suggests that the new risk model could mean far fewer Americans — as many as 40% less than current calculators say — would be candidates for cholesterol-lowering drugs to prevent cardiovascular disease.

To reach this conclusion, published Monday in a JAMA Internal Medicine study, researchers analyzed data from 3,785 adults who were 40 to 75 years old and took part in the National Health and Nutrition Examination Survey from January 2017 to March 2020. Their 10-year risk of artery-narrowing cardiovascular disease was computed using the AHA’s Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations from 2023 and then compared to risk estimates using the previous tool from 2013, the Pooled Cohort Equations (PCE) on which current guidelines are based.

Those 2013 equations were widely criticized as overestimating risk. The 2023 version, drawing on billing and electronic health record data from a more diverse real-world population, incorporated current statin use as well as metabolic and kidney diseases.

Chiadi Ndumele, chair of the American Heart Association’s CKM Scientific Advisory Group, emphasized that the actual PREVENT risk thresholds for statin use in cardiovascular prevention will need to be decided in clinical guidelines, and that has not yet occurred. He also acknowledged criticism of the earlier risk model.

“We updated the AHA risk prediction model to PREVENT reflecting the growing influence of inter-related metabolic risk factors (obesity, diabetes, metabolic syndrome) and chronic kidney disease on cardiovascular disease risk,” Ndumele, director of obesity and cardiometabolic research at Johns Hopkins University, told STAT in an email. “It is therefore not surprising that the investigators found about twice the predicted event rate for the PCEs vs. PREVENT, reflecting this difference.”

Under the current guidelines, most people with a 10-year risk of 7.5% or more for developing cardiovascular disease are advised to take a statin, while at a 5% risk, they’re told only that they and their doctors should consider doing so.

“Analyses are underway,” Ndumele said. “Guidelines will have to consider whether and how to update recommendations to include PREVENT risk thresholds to guide clinical decision making.”

What’s changed in the JAMA Internal Medicine analysis is how many people might be at risk, based on the new components put into the calculator. Overall, 4% of people had a 10-year risk of developing cardiovascular disease, compared to the 8% previously predicted by the PCE. The number of adults recommended for statins could drop from 45.4 million to 28.3 million.

Race, now recognized as a social not biological construct, was excluded in the newer equations. That meant 5.1% of Black adults were computed to be at risk, compared to 10.9% from the previous calculator. For older adults ages 70 to 75, the proportion at risk was 10.2%, down from 22.8%.

In a paradox, the study found that while fewer people might be eligible for statins, which now can cost as little as $40 a year, the estimates also say most people who would be advised to take them aren’t doing so.

“The prior risk equations and the PREVENT equations that we focus on in this study really seek to give doctors and patients sort of a starting percentage to say, is it worth having a conversation about statins?” lead study author Timothy Anderson, a primary care physician and an assistant professor of medicine at University of Pittsburgh Medical Center, told STAT. “When we’re seeing risk rates cut in half, I think that really is something that’s likely to impact how doctors and patients talk about these meds.”

The biggest predictor of risk remains age, Anderson said. “If you’re a borderline risk now, you’re likely to be higher risk in five years. And that’s a complicated set of conversations for primary care doctors and patients to have.”

That concerns Steven Nissen, a cardiologist at the Cleveland Clinic, who was not part of the study. “Age is the most powerful factor in the calculators, so if you wait until somebody is 60 or 65, you’re playing catch-up,” he said. “I tend to lean toward treating rather than not treating when it’s a borderline case, but only when the patient and I have a conversation.”

Nissen has been leading an effort in collaboration with AstraZeneca to make the 5-milligram dose of its drug, rosuvastatin, available without a prescription. He urged shared decision-making between doctor and patient, aware that busy primary care physicians may be pressed for time.

“Good medicine involves judgment. And the calculator is not a replacement for good medical judgment, which may come to a different conclusion,” he said. “I’m not very supportive of either calculator because I think that in general, it’s good to have a lower LDL,” or “bad” cholesterol.

There are a multitude of factors affecting cardiovascular health, and statins are just one piece, said Gregg Fonarow, chief of cardiology at UCLA, citing the AHA’s recent projection that 61% of the U.S. population will likely have cardiovascular disease. He did not take part in the current study.

“So many cardiovascular events are preventable, not just through medication but through lifestyle modification. We need to do such a better job with prevention,” Fonarow said. “This really represents an opportunity to use the new enhanced PREVENT risk score and better inform individuals of risk, but importantly, not just for 10-year risk, but their lifelong risk for disease.”

Ndumele said PREVENT will help guide use of preventive therapies beyond statins, relevant for people with cardiovascular-kidney-metabolic syndrome, a disorder in which metabolic risk factors, chronic kidney disease, and the cardiovascular system interact to cause multi-organ dysfunction and poor cardiovascular outcomes.

“I think the challenge with this paper is the assumption that the same threshold will be used for the recommendation of statin use,” Ndumele said. “Risk estimates from PREVENT are much closer to what is observed in reality than they were for PCEs, but there is need for discussion about the optimal risk threshold for preventive statin use in guidelines.”

Nissen said any changes should be thought through carefully, with this caveat: “The take-home message is that any of these calculators are the best guess about risk,” he said, “but the decision to treat is different from simply calculating a risk.”

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