On November 13, the US Preventive Services Task Force (USPSTF) released the final recommendations and evidence summary for the use of statins for the primary prevention of cardiovascular disease (CVD) in adults.
The recommendations are available online at www.uspreventiveservicestaskforce.org
The final recommendations, published in the Journal of the American Medical Associations (JAMA), are largely consistent with 2015 draft recommendations. They update 2008 recommendations, which had not previously recommended widespread statin use for CVD prevention.
Main points of the recommendations are as follows:
Low- to moderate-dose statins in adults aged 40 to 75 years who do not have a history of CVD but who do have one or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and who have a 10% or greater risk of having a CVD event (myocardial infarction or stroke) over the next 10 years (B recommendation).
On the basis of a discussion with patients, clinicians should selectively offer low- to moderate-dose statins to adults aged 40 to 75 years who do not have a history of CVD but who have one or more CVD risk factors and a 7.5% to 10% risk for a CVD event in the next 10 years (C recommendation).
Evidence is insufficient for the benefits and harms of starting statins in adults 76 years and older (I statement).
Clinicians are advised to determine 10-year CVD risk using the pooled cohort equations developed by the American College of Cardiology/American Heart Association (ACC/AHA).
The new recommendations do not apply to patients at very high risk, such as individuals with familial hypercholesterolemia or those with low-density lipoprotein (LDL) levels over 190 mg/dL.
In a series of editorials, experts weighed in about the new recommendations. Their responses reveal the contentious debate about statins for CVD prevention and emphasize persisting gaps in the evidence base.
Such gaps have led to four different sets of major recommendations on statins, note Philip Greenland, MD, and Robert Bonow, MD, MS, both from Northwestern University Feinberg School of Medicine, Chicago, Illinois. Guidelines differ regarding specific LDL targets and specific treatment initiation thresholds, mainly because supporting evidence is lacking.
Research gaps also exist about the benefits of statins for prevention of CVD
Rita Redberg, MD, MSc, from the University of California San Francisco and Mitchell Katz, MD, from the Department of Health Services, Los Angeles, California, and Deputy Editor of JAMA, take matters a step further.
"[T]he evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation," they write.
They take particular issue with the evidence regarding possible harms of statins. All but one of the trials included in the evidence review were sponsored by industry, which may report greater benefit and fewer adverse effects than studies without commercial ties. Many studies do not report on common harms that can affect quality of life, such as muscle pain and weakness. Some studies have suggested increased risk for cognitive dysfunction and diabetes, with evidence particularly strong for the latter, they explain.
Anne Marie Navar, MD, PhD, and Eric Peterson, MD, MPH, both from Duke Clinical Research Institute, Durham, North Carolina, point out that trial data are a good start, but they cannot encompass the full range of patient experience.
Because atherosclerosis develops over decades, assessing long-term rather than 10-year risk in younger adults may identify those who could benefit from early, aggressive therapy. However, more research is needed to understand the cumulative risks and benefits of long-term statin therapy in individuals under age 40 years.
They also note other important gaps in the literature, including adequate identification of those age 40 to 75 years and those over age 75 years who could benefit most from therapy.
Not surprisingly, editorialists differed on how to approach clinical care given continued gaps in the literature.
Because studies under-represent older patients, Dr Greenland and Dr Bonow suggest extrapolating data from younger patients to otherwise healthy adults over age 75 years.
"It is not necessary to stop statin therapy when a 75-year-old turns 76," they write.
Dr Redberg and Dr Katz are wary of using statins for primary prevention, given the relative dearth of evidence demonstrating that the benefits over time outweigh harm.
"Given the serious concerns about the harms of the reliance on statins for primary prevention, it is in the interest of public health and the medical community to refocus efforts on promoting a heart-healthy diet, regular physical activity, and not smoking," they write.
Dr Navar and Dr Peterson wonder what the default should be for patients who fall in the gray zone, for whom the guidelines and research are less clearcut. For a patient with high LDL but low 10-year CVD risk due to young age, should the default be to treat, not treat, or use an approach somewhere in between, based on clinical opinion?
"[I]t may be reasonable to consider offering therapy to younger populations even before the benefits are fully confirmed. This consideration is based on an evaluation of the potential benefits, risk, and costs of statin treatment," they write.
In the end, all three sets of editorialists emphasize the need for shared decision making and deferring to clinical judgment for difficult treatment decisions.
"Gaps in the evidence provide opportunities for clinicians to practice the art of medicine and engage with patients in shared decision making regarding strategies for CVD prevention," Dr Navar and Dr Peterson conclude.
One or more authors reports consulting, grants, and/or royalties from one or more of the following: the Institute for Clinical and Economic Review, National Institutes of Health and/or UpToDate. Dr Epling served on a technical expert panel that reviewed protocol of a study related to comparative effectiveness of lipid-modifying agents. Dr Greenland, Dr Bonow, and Dr 
JAMA. 2016;316:1997-2007, 2008-2024, 1977-1979, 1979-1981, 1981-1983.
Recommendation statement
Importance Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults.
Objective To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in adults.
Evidence Review The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.
Conclusions and Recommendations The USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).
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