New USPSTF Statin Guidance: Familiar Advice, Some Holes to Fill

The United States Preventive Services Task Force (USPSTF) has updated its recommendations around the use of statins in the primary prevention of cardiovascular disease after reviewing the latest evidence supporting benefits and harms. Cardiologists working in this space will find that the new document is not much changed from the last USPSTF statin advice in 2016.

For adults ages 40 to 75, statins for preventing CVD or all-cause death make sense in those who have no history of CVD, but do have one or more risk factors and a 10-year CVD risk of 10% or greater—in this group, statins have at least a “moderate net benefit” and the recommendation itself is based on “moderate certainty” (Grade B).

For that same age group, with the same baseline risk and history but a lower 10-year risk (ranging from 7.5% to less than 10%), the same recommendation can be made, this time with moderate certainty and an expectation of “at least a small net benefit” (Grade C).

To decide which of these two groups a given patient falls into, clinicians can use the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations to estimate 10-year risk of CVD, the authors say, noting that this tool remains the only US-based risk estimator that has been externally validated, with different equations for Black and non-Black adults, although the document also acknowledges that race is an “imperfect proxy for social determinants of health and the effects of structural racism.”

Where the role for statins is less clear-cut is for adults 76 and older: in this group, the USPSTF concludes (as it did back in 2016) that the evidence is insufficient for teasing out the balance of benefit and harm (Grade I, indicating “inconclusive”).

USPSTF member and primary care physician John B. Wong, MD (Tufts Medical Center, Boston, MA), speaking with TCTMD, agreed that the 2022 recommendations are “fairly consistent” with the last iteration. What’s new is the updated evidence base, which now includes 26 studies—23 of which are clinical trials—representing over half a million patients, Wong said.

Also more evident this time around are the extent of the inequities and disparities, not only in the rates of cardiovascular disease, stroke, and myocardial infarction, but also in access to and use of statins among patients who are Hispanic, Black, or Asian, Wong observed.

“We're calling out for more research to understand that inequity,” said Wong, “but in the meantime, we really want healthcare professionals who are taking care of these kinds of adults to pay particular attention to them and to try to inform them about the benefits and about the opportunity to prevent that first stroke or first heart attack, which can be a lifelong devastating disease to cope with for adults as well as their families.”

Not Enough New?

The updated recommendations, published today in JAMA, are accompanied in that journal by the evidence report, a patient page, and an editorial by Ann Marie Navar, MD, PhD and Eric D. Peterson, MD, MPH (both University of Texas Southwestern Medical Center, Dallas). Additional editorials appear in other JAMA journals.

My job as a cardiologist isn't to keep you from having a heart attack in the next decade. My job should be to keep you from having a heart attack over your lifetime. Ann Marie Navar

Elaborating on her JAMA editorial to TCTMD, Navar said she was “fairly disappointed” to see that the new recommendations adhered so closely to the 2016 document with their focus on 10-year risk to guide therapy. “Lipid and cholesterol, which are what statins actually lower and how they prevent heart disease, aren't mentioned at all, except as a kind of extra risk factor that you have to have in addition to 10-year risk,” she said. “I think that our pendulum has swung so far away from biology here towards risk there's really just a lot of potential for missing important groups for treatment.”

The missed opportunity in this update, she continued, was to incorporate the newer information that has emerged in the past 5 years, especially the strong epidemiologic data showing that cardiovascular risk starts to go up with LDL cholesterol levels over 100 mg/dL.

“I wish [these guidelines] were slightly more nuanced, more focused on the biology, and incorporated cholesterol into that, and that they went beyond 10-year risk,” she said. “My job as a cardiologist isn't to keep you from having a heart attack in the next decade. My job should be to keep you from having a heart attack over your lifetime.”

Responding to Navar’s concerns, Wong agreed on the importance of lifetime risk, but said more research is needed not only to appreciate the effects of earlier statin initiation, but also to understand how individuals think about 10-year risk versus lifetime risk to inform the kind of shared decision-making advocated in the recommendations.  

“Ideally we would understand better the benefits and harms of longer duration of use,” he said. “I think the editorial is implying that perhaps we should be thinking about possibly starting them at an even younger age and . . . we don't have good data about that. But we're calling for additional research into whether or not statins would be beneficial for those under 40.”

Navar acknowledged that the USPSTF does “a great, comprehensive review of the evidence,” and that its reliance on the 10-year risk is similar to that of the ACC/AHA guidelines. “But I think it's time for not only the USPSTF but also the ACC/AHA, and European guidelines for that matter, to start going beyond 10-year risk,” she urged.

Guideline Overlap

Wong pointed out that since this document is focused on the use of statins in people with no signs or symptoms of disease, it’s really aimed at a primary care audience. And while there are key differences between these recommendations and those set out in the ACC/AHA primary prevention guidelines, both documents, he stressed, reinforce the importance of shared decision-making with patients. The ACC/AHA guidelines, the new USPSTF recommendations, and even the Veterans Affairs/Department of Defense guidelines released last year all use different 10-year risk thresholds for determining when a statin should or could be initiated, Wong noted.

What’s important to remember is that these are population-based risk estimates, he said. “For any individual person or adult, it's in some sense a guesstimate or an estimate, and there's some uncertainty around that. This is where for me, a high-quality decision at the individual, personal level involves a detailed discussion about . . . how that patient feels, and their preferences and values about taking a medication or changing their diet or improving their physical activity level. All of those go into the mix in terms of helping that patient achieve their optimal cardiovascular health.”

For physicians wanting to delve deeper into the details of where the guidelines do and don’t overlap, Neil J. Stone, MD, and Philip Greenland, MD (both Northwestern University Feinberg School of Medicine, Chicago, IL), along with Scott M. Grundy, MD, PhD (University of Texas Southwestern Medical School), spell those out in an editorial published simultaneously in JAMA Cardiology. There are “substantial points of agreement,” they note, but also some striking differences, most notably the use of a 10-year CVD risk of 10% or greater for adults ages 40 to 75 (the ACC/AHA document specifies a 20% risk or greater).

“Generally speaking, I would still direct people to the ACC/AHA guidelines, because they're much more comprehensive and much more in-depth than the USPSTF recommendations,” which don’t cover patients with severe hyperlipidemia or provide in-depth advice for patients with diabetes, Navar said.

The latter is a group also singled out by Salim Virani, MD, PhD (Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX), whose editorial appears in JAMA Network Open. In an email to TCTMD, he points out that the USPSTF recommendations “lump all adults patients with diabetes in the same bucket as the general population whereas ACC/AHA guidelines separate them. This allows more-aggressive treatment of patients with diabetes who we know are at a higher risk compared with the general population. The ACC/AHA guidelines also allow tailoring intensity of statin therapy based on other characteristics of a patient with diabetes which increase their cardiovascular risk.”

Unlike today’s document, the ACC/AHA guidelines allow for “risk enhancers,” such as family history, metabolic syndrome, inflammatory disorders, and more, to be considered in decision-making and also provide strong recommendations for the use of coronary artery calcium score.

Beyond those specifics, Virani continued, “I would emphasize that we already know that a large number of patients who should be receiving statin therapy are not receiving it even based on the more-conservative USPSTF recommendations. With the CVD pandemic, we as clinicians need to treat our patients and will save lives by following either of these two guidelines but we need start and not to take our foot off the pedal.”

Wong acknowledged that while the aim of the USPSTF is to provide a careful evidence review and advice to physicians in primary care, the document and particularly the grade of its recommendations are used by insurers for the purposes of paying—or not—for different therapies. A B-grade recommendation, for example, would likely be covered by private insurers without a co-pay.

“I want to be very clear,” he said. “The US Preventive Services Task Force, when it develops its recommendations, only looks at the evidence for benefits and harms, and we're doing an assessment at the population level based on the relative benefits versus the harms and our certainty around that evidence. . . . We recognize that payment and insurance coverage is important to many people, but we want to be very clear that our recommendations are based on the evidence and solely on the evidence.” Writing group members are “aware” of coverage decisions, Wong added, but they do not influence the process.