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For higher-risk adults without prior cardiovascular disease (CVD) events, the U.S. Preventive Services Task Force (USPSTF) continues to broadly recommend statins for primary prevention while differing from other American guidelines in certain key aspects.

In a finalized statement , the USPSTF maintained distinct recommendations for statins determined by a person's age and 10-year CVD risk according to the pooled cohort equations (PCEs):

• B recommendation for statins in adults age 40-75 years who have one or more CVD risk factors and an estimated 10-year CVD risk of 10% or greater (based on evidence review suggesting with moderate certainty that statins have at least a moderate net benefit in this group)

• C recommendation for selective use of statins in adults age 40-75 years who have at least one CVD risk factor and an estimated 10-year CVD risk of 7.5-10% (based on evidence review suggesting moderate certainty that statin use has at least a small net benefit in this group)

• I statement of insufficient evidence regarding the benefits and harms of statin use for primary prevention in people older than 76 years

Despite being consistent with the USPSTF's 2016 recommendations on the subject, the latest update takes away language about the preferred low-to-moderate dosing of statins in people with no history of CVD. This could be attributed to a lack of data, as a review of the literature showed most statin trials tested a moderate-intensity statin.

Carol Mangione, MD, MSPH, of the David Geffen School of Medicine at UCLA, and the rest of the USPSTF writing group urged that future trials be conducted that directly compare higher-versus-lower-intensity statin therapy and are powered to assess clinical outcomes.

The new guidelines are also notable for the 7.5% PCE threshold for statin initiation -- a slightly more conservative choice compared with the 5% risk cutoff for shared decision-making on statins as endorsed by the 2018 American Heart Association/American College of Cardiology guideline.

"One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment," said Neil Stone, MD, of Northwestern University Feinberg School of Medicine in Chicago, writing in an editorial in .

Furthermore, given that the PCEs were designed to predict CVD risk on the population level decades ago, they are an "imperfect" way to assess absolute risk at the individual level today, another group explained: "The PCE was derived and validated in studies that enrolled individuals (mostly White males) between 1968 and 1990. Thus, the PCE does not reflect the recent decreases in rates of CVD that have accrued owing to population-wide health improvements from reduced rates of smoking, shifts in dietary patterns and exercise, and blood pressure control," wrote Rita Redberg, MD, MSc, of the University of California San Francisco, and two fellow JAMA Internal Medicine editors in a published in that journal.

The PCEs alone also ignore important risk modifiers such as coronary artery calcium, familial hypercholesterolemia, presence of metabolic syndrome, premature menopause, history of preeclampsia, and South Asian ancestry.

Additionally, some clinicians complained that basing statin use on the PCE cut points of 5%, 7.5%, 10%, and 20% may be arbitrary to begin with. This could mean that clinicians are not prescribing treatment to people who may benefit from it.

"Waiting for a person to reach an age when their 10-year predicted CVD risk exceeds a certain arbitrary threshold before recommending a statin allows atherosclerosis to proceed unchecked for decades. It is time to realign statin guidelines with the biology of atherosclerosis by refocusing on the risk factor these medications treat, elevated [LDL cholesterol] level, and considering CVD prevention over a lifetime, not 10 years," urged JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, and Eric Peterson, MD, MPH, both of the University of Texas Southwestern Medical Center in Dallas.

"While using estimated 10-year CVD risk may be helpful to guide patient-clinician shared decision-making, it should not continue to be the primary guide to identify statin candidates," Navar and Peterson wrote in a . They reasoned that other primary prevention therapies -- such as blood pressure-lowering treatment and smoking-cessation therapies -- do not hinge on a 10-year risk estimate.

In any case, the low use of statins in current practice leaves room for improvement, according to Salim Virani, MD, PhD, of Michael E. DeBakey Veterans Affairs Medical Center in Houston.

"Clinical inertia, statin-associated adverse effects, and social media all play roles in suboptimal use of statin therapy in clinical practice. System-level interventions are needed to assist clinicians in implementing evidence-based statin therapy use in primary prevention. Thoughtful conversations are also needed with patients to counter the misinformation about statin therapy that is pervasive in social media," he suggested in his .

On the other hand, Redberg's group cautioned that statins are of uncertain net benefit for primary prevention in people without CVD.

"Although statins lower LDL cholesterol in individuals, investments at the community level to construct a more salubrious environment that enables healthy eating and promotes physical activity are likely to have more widespread multiplicative and pleiotropic effects on the biological and psychosocial risks of CVD, as well as on improving quality of life," according to these editorialists.

The USPSTF's evidence review included 26 randomized and observational studies with follow-up averaging 3 years.

Investigators did not find statins to be associated with serious adverse events such as myalgia or elevated alanine aminotransferase level. However, one trial did link high-intensity statin therapy to incident diabetes.