Nonstatin use has skyrocketed in the past decade, rising by 124 percent and causing a 364 percent increase in nonstatin-related expenditures, according to a report published in the Journal of the American Heart Association this month.

Statins might be the “cornerstone” of atherosclerotic cardiovascular disease (ASCVD) risk reduction, Joseph A. Salami, MD, MPH, and colleagues wrote, but they’re not the end-all, be-all of lipid-lowering therapies. Some heart patients experience side effects—like liver damage, muscle pain and neurological issues—that make it impossible to take statins. Others can’t take the drugs due to genetic conditions that cause blood cholesterol levels to skyrocket past the point of statin intervention.

Those who aren’t prescribed statins have the option of taking nonstatin medications, Salami and co-authors wrote, which include fibrates, cholesterol absorption inhibitors, bile acid sequestrant, cholesterol-lowering combinations, niacin, omega-3 fatty acids and PCSK9 inhibitors.

“The clinical utility and application of nonstatin lipid-lowering therapies for ASCVD risk reduction, however, remain uncertain,” the authors wrote. “To date, time trends in the utilization of nonstatin use and associated expenditure at a national level remains unknown.”

Though several agents, including the American Heart Association and American College of Cardiology, have released suggestions  in recent years to guide the prescription and use of nonstatins, evidence remains weak and uncertain, Salami et al. said.

Salami’s team used the Medical Expenditure Panel Survey to estimate national trends in nonstatin use and cost among middle-aged adults, focusing on the decade between 2002 to 2003 and 2012 to 2013. In 2002, there were roughly three million nonstatin users in the U.S., they reported—a figure that had jumped to eight million by 2013.

The trend was even more apparent in patients with ASCVD, whose nonstatin consumption increased from 7.5 percent in 2002 to 13.9 percent in 2013, after peaking at 20.3 percent in 2006.

One of the more popular methods of integrating nonstatins into a medication routine involves mixing them with traditional statins, Salami and colleagues wrote. High-intensity statin users prescribed a nonstatin as an adjunct medication grew to 15.9 percent of the population pool by 2013, while low-to-moderate statin users reached 9.7 percent.

Women and racial and ethnic minorities were the least likely to take statins. Joining those groups were the uninsured, who saw an increase from per-user nonstatin expenditures of $550 to $992 between 2002 and 2013. Total nonstatin expenditures rose from $1.7 billion in 2002 to $7.9 billion in 2013.

“Nonstatin lipid-lowering therapies are frequently used among U.S. adults with and without ASCVD,” Salami and co-authors said. “These findings should guide pragmatic discussions among stakeholders for appropriate use of current and upcoming nonstatin lipid-lowering therapies, especially for ASCVD risk management."