Consider age, sex when determining need for statins, study suggests

Cholesterol treatment recommendations could be improved by using age- and sex-specific thresholds for cardiovascular disease (CVD) risk, a study found.

To determine the potential impact of incorporating age- and sex-specific CVD risk thresholds into current cholesterol guidelines, researchers used data from the Framingham Offspring Study, including 3,685 participants who were free of CVD.

Baseline characteristics such as blood pressure, diabetes status, smoking, and lipid levels were used to calculate participants' estimated 10-year CVD risk based on the Pooled Cohort Equations. Statin treatment recommendations were based on the 2014 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines. The recommendation for statin therapy was assessed first for all patients, and then by age-specific (40 to 55 years, 56 to 65 years, and >65 years) and sex-specific subgroups.

Adults were followed prospectively for 10 years for new-onset CVD events, defined as a nonfatal myocardial infarction, coronary heart disease death, fatal or nonfatal stroke, peripheral arterial disease, or heart failure. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the guideline's statin treatment recommendations were calculated based on a patient's subsequent CVD events.

Results appeared in the March Journal of the American College of Cardiology.

Basing statin therapy recommendations on a 10-year fixed risk threshold of 7.5% resulted in lower statin use among women than men (63% vs. 33%; P<0.0001), the authors found. But treatment was still recommended in 90.3% of patients ages 66 to 75 years. The fixed 7.5% threshold also had relatively low sensitivity for capturing 10-year events in women and men ages 40 to 55 years.

The authors noted that sensitivity of the recommendations was substantially improved when the 10-year risk threshold was reduced to 5% in those ages 40 to 55 years, which changed sensitivity from 36% to 61% in women and 49% to 71% in men. Among adults ages 66 to 75, specificity was poor, 18% in women and 3% in men, but when the risk threshold was raised to 10% in women and 15% in men, specificity significantly improved to 34% in women and 14% in men. There was only a small loss in sensitivity, from 95% to 87%, in women, and none in men, with 96% at both thresholds.

The authors noted that the new ACC/AHA cholesterol guidelines substantially increased the number of individuals for whom statin therapy is recommended. They noted 2 key concerns regarding the use of a fixed risk threshold. First, the 7.5% threshold adopted by the current cholesterol guidelines may not be the best for determining if young adults should take statins. The results of this study supported the use of the optional 5% threshold in the current ACC/AHA guidelines for identifying adults ages 40 to 55 who are at risk for premature CVD, the authors said.

Second, while statin therapy was recommended for the vast majority of older adults ages 66 to 75, this affected significantly more men than women. Since 9 in 10 older men had a 10-year risk of 7.5%, the specificity of this recommendation was poor, which would lead to high rates of potentially unnecessary statin treatment. The guideline specificity in older men can be substantially improved with no impact on sensitivity by raising the treatment threshold to 15%, the authors wrote.

A slight adjustment of classification thresholds could improve the guideline, the authors concluded. “We acknowledge that there is no such thing as a perfect threshold; improved sensitivity for predicting future events comes with the tradeoff of reduced specificity and vice-versa,” they wrote. “As a result, providers and patients must weigh potential risks of statin therapy (including cost considerations) against their perceived benefit when deciding whether or not to use statin therapy for primary prevention.”