USPSTF issues recommendations on statins for primary prevention

The U.S. Preventive Services Task Force (USPSTF) issued a recommendation statement earlier this week on use of statins for primary prevention, focusing on adults ages 40 and older with no history, signs, or symptoms of cardiovascular disease (CVD).

The statement, which updates the USPSTF's 2008 recommendation on screening for lipid disorders in adults, was based on a systematic review of the evidence on benefits and harms of screening for and treating dyslipidemia and benefits and harms of statins in reducing cardiovascular disease (CVD) events and mortality in adults with no CVD history. In addition, the review looked at whether statin benefits varied by patient subgroup, clinical characteristics, or dosage, and it examined the benefits of different treatment strategies in adults at least 40 years of age who had no history of CVD events.

The recommendations do not apply to patients with very high low-density lipoprotein cholesterol levels or known familial hypercholesterolemia, the USPSTF said. Both the review and the recommendation statement were published online Nov. 13 by JAMA.

The USPSTF's recommendations are as follows:

• Low- to moderate-dose statins should be started in adults 40 to 75 years of age who have no history of CVD but have at least 1 CVD risk factor (i.e., dyslipidemia, diabetes, hypertension, or smoking) and a 10-year CVD event risk calculated at 10% or more. This is a grade B recommendation, meaning that there is a high certainty that the net benefit is substantial and clinicians should offer or provide this service.
• Low- to moderate-dose statins should be selectively offered to adults 40 to 75 years of age who have no history of CVD but have at least 1 CVD risk factor and a 10-year CVD risk calculated at 7.5% to 10%. This is a grade C recommendation, meaning that there is a high certainty that the net benefit is moderate or moderate certainty that the net benefit is moderate to substantial and clinicians should offer or provide this service.

The USPSTF said clinicians should use the American College of Cardiology/American Heart Association Pooled Cohort Equations to calculate 10-year risk of CVD events. Although this calculator has generated some controversy, it is the only U.S.-based prediction tool for CVD risk to date that has been validated externally in other U.S. populations, the USPSTF noted. The Task Force also found that the evidence was insufficient to determine the benefits or harms of statin initiation in adults ages 76 years and older. The USPSTF said that more research is needed on the efficacy of screening and treatment in patients ages 20 to 39 years and on the potential long-term harms of statin therapy, among other areas.

One editorial accompanying the study applied the USPSTF recommendations to 2 hypothetical patients to demonstrate the usefulness and limitations of statin guidelines, noting that treating according to estimated risk rather than high cholesterol levels has been challenging for physicians. “For patients in the gray area not covered by the guidelines, clinicians should be cautioned against adopting either a ‘treat none’ or a ‘treat all’ strategy,” the editorialists wrote. “Rather, 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.”

Another accompanying editorial compared the USPSTF recommendations with 4 other recent major guidelines on statin use and summarized their differences and similarities. For example, the guidelines strongly agree on the effectiveness of statins and on their broad treatment indications but disagree on specific low-density lipoprotein targets due to the observational level of the existing evidence in that area, as well as on thresholds for initiation of treatment, the editorialists said.

The editorialists noted several take-home messages, including the critical importance of ensuring at least some statin use in higher-risk patients, the possible utility of additional testing to help treatment decisions in the absence of clear risk thresholds, the reasonableness of extrapolation of data in younger patients to healthy older patients, and the necessity for clinical judgment and patient input.

A third editorial looked at the contentious nature of the statin debate and stressed the possible consequences of statin use for primary prevention, noting that while the USPSTF did a good job summarizing the existing evidence, the limitations of the evidence needed more attention. “In deciding on any therapy, it is important to understand the risks and benefits, particularly for healthy people. It is incumbent on clinicians to be sure that before recommending that a patient take a daily pill that has multiple adverse effects, there is evidence that the medication will lead to a better quality of life, longer life, or both. Such evidence is lacking for statins in primary prevention,” the editorialists wrote. “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.”

Also in statin news but regarding secondary rather than primary prevention, an unrelated retrospective cohort analysis published online Nov. 9 in JAMA Cardiology looked at the association between all-cause mortality and statin intensity in the Veterans Affairs system among patients with atherosclerotic cardiovascular disease (ASCVD). Among 509,766 eligible adults with ASCVD at baseline with a mean age of 68.5 years, 150,928 (29.6%) were receiving high-intensity statin therapy, 232,293 (45.6%) were receiving moderate-intensity statin therapy, 33,920 (6.7%) were receiving low-intensity statin therapy, and 92,625 (18.2%) were receiving no statins.

The authors found a graded inverse association over a mean follow-up of 492 days between statin intensity and mortality. Mortality rates at 1 year were 4.0% in the high-intensity group, 4.8% in the moderate-intensity group, 5.7% in the low-intensity group, and 6.6% in the no-statins group. For patients receiving high- vs. moderate-intensity statins, the hazard ratio for death was 0.91 (95% CI, 0.88 to 0.93) after adjustment for propensity to receive high-intensity statins, with a similar magnitude of benefit (incident cohort hazard ratio, 0.93; 95% CI, 0.85 to 1.01). The hazard ratio was 0.91 (95% CI, 0.87 to 0.95) in older patients, that is, those ages 76 to 84.

The authors acknowledged that they could not completely adjust for potential confounders or determine causes of death, among other limitations, but concluded that in real-world practice, intensity of statin therapy is inversely related to mortality. “These findings suggest there is a substantial opportunity for improvement in the secondary prevention of ASCVD through optimization of intensity of statin therapy,” they wrote.

An accompanying editor's note stressed the importance of the finding of benefit in patients older than age 75 and said that while statin therapy should be very individualized, “we find these findings confirmatory that high-intensity statin therapy when appropriate is beneficial for secondary prevention, and these benefits are seen even in older persons.”