Better statin therapy with age- and sex-specific risk thresholds

By Will Boggs MD

NEW YORK (Reuters Health) - Using age- and sex-specific risk thresholds could result in improved cholesterol treatment recommendations, researchers report.

"Clinicians should take into consideration a patient's age and sex when considering patients for statin therapy to reduce risk of heart disease," Dr. Ann Marie Navar-Boggan from Duke University Medical Center in Durham, North Carolina, told Reuters Health by email. "Many older adults who qualify for lipid-lowering therapy based on age and sex alone may not benefit from therapy. On the other hand, relying on a threshold of 7.5% in younger adults will miss up to one in two who will have heart disease in the next 10 years."

The new findings were presented on Sunday, March 15, at the scientific sessions of the American College of Cardiology in San Diego, California. They also appear in a report published online March 2 in the Journal of the American College of Cardiology.

New American College of Cardiology/American Heart Association (ACC/AHA) blood cholesterol guidelines strongly recommend statin therapy consideration in adults with a 7.5% or higher risk of experiencing a cardiovascular event over the next decade, with an option also to treat those with a risk between 5% and 7.5%.

Adherence to the new guidelines would increase the number of adults recommended for statin therapy by nearly 13 million, with 80% or more of adults aged 60 years and over receiving therapy, Dr. Navar-Boggan and colleagues write in their report.

But it remains unclear whether the thresholds would actually result in treating most of those who would subsequently develop an event (high sensitivity) and avoiding unnecessary treatment among those who would not (high specificity), they add.

Based on data from the Framingham Offspring Study, the team found that for individuals aged 40 to 55 years, lowering the risk threshold from 7.5% to 5.0% would markedly improve sensitivity (from 35% to 61% in women and from 49% to 71% in men) while reducing specificity somewhat less (from 90% to 78% in women and from 71% to 56% in men).

For those aged 56 to 65 years, the 7.5% threshold would identify nine in 10 men who would develop cardiovascular disease over the next 10 years, but fewer than half of women, they estimate; reducing the threshold to 5.0% for women would improve the sensitivity from 49% to 65%.

In the oldest age group examined (66 to 75 years), doubling the threshold for men from 7.5% to 15% would reduce the fraction recommended for statin therapy from 97% to 89% without changing sensitivity but with an improvement in specificity from 3% to 14%.

Moving the threshold from 7.5% to 10% for women would reduce the sensitivity from 95% to 87% but would nearly double specificity (from 18% to 35%).

"Using more age- and sex-specific thresholds, we can improve the overall sensitivity across all adults by 6%, meaning we can catch an additional 6 in 100 adults who will develop heart disease in the next 10 years," Dr. Navar-Boggan said. "However, when you look in certain populations we get much greater improvements. For example, in young men, we can improve the sensitivity from 48% to 71%. Thus, using a lower threshold in young men, we can identify an additional 23 men (in 100) ages 40-55 who will go on to have heart disease in the next 10 years, and target them for more aggressive intervention."

"The guidelines emphasize that adults should engage in an informed discussion with their doctor about the potential risks and benefits of statin therapy, which includes a discussion of other risk factors not covered in these models," Dr. Navar-Boggan concluded. "Using age and sex specific thresholds can help give providers and patients 'smarter' starting points."

Dr. Joseph Yeboah from Wake Forest School of Medicine in Winston-Salem, North Carolina, recently considered the implications of the new ACC/AHA guidelines in a multi-ethnic cohort.

"Besides making the cholesterol guidelines more complicated for physicians, age- and sex- specific threshold would not make cardiovascular disease (CVD) risk prediction a perfect science," he told Reuters Health. "It is currently impossible to identify all the 'right' individuals for preventive treatment."

"I commend the authors for at least beginning the conversation of whether age- and sex- specific thresholds can potentially be useful in changing statin eligibility in the USA and also improving guideline treatment performance," Dr. Yeboah said. "However, this study is by no means conclusive given the significant limitations."

In particular, he said, "the cohort is not representative (all whites) and the constituents of the CVD composite outcome used in this study is vastly different from that used in the cholesterol guidelines."

"Age and male sex are major traditional risk factors for CVD," Dr. Yeboah added. "It is therefore not surprising that varying the thresholds within age groups and sex may help reduce the number of individuals eligible for treatment. However, this may not necessarily be a good public health approach for a nation if in the end it does so by not treating a large number of 'right' individuals with a relatively safe, cheap, and efficacious drug."

SOURCE: https://bit.ly/1ByEO33

J Am Coll Cardiol 2015.