Patients who do not tolerate or respond to higher-intensity statins may benefit from lower-intensity statin therapy along with either bile acid sequestrants or ezetimibe, findings from a study published online Feb. 11 in Annals of Internal Medicine suggest.

Researchers led by Kimberly Gudzune, MD, MPH, of Johns Hopkins University School of Medicine in Baltimore, sought to compare a combination of lower-intensity statins with high-intensity statin monotherapy for benefits, harms and adherence. They conducted a review of randomized clinical trials through July 2013 and included the trials with adults at high risk for atherosclerotic cardiovascular disease (ASCVD)—defined as having a low-density lipoprotein (LDL) cholesterol level of 190 mg/dl or higher, pre-existing ASCVD or diabetes mellitus—that compared the lower-dose and higher-dose statin regimens.

Data from 36 studies suggested that using low-intensity statins along with a bile acid sequestrant decreases LDL cholesterol between 0 percent and 14 percent more than using one mid-intensity drug in patients with hyperlipidemia. Mid-intensity statin use along with ezetimibe (Zetia, Merck) decreased LDL cholesterol between 5 percent to 15 percent more than high-intensity monotherapy in patients with ASCVD and 3 percent to 21 percent more in patients with diabetes mellitus.

There was not enough evidence to assess long-term clinical outcomes, adherence and harmful effects for any of the therapy regimens or to evaluate fibrates, niacin or omega-3 fatty acids.

The authors acknowledged that some of the trials did not last long, had many dropouts, were not blinded and did not evaluate long-term clinical benefits or harms. However, they urged caution with the lower-intensity regimens.

“Clinicians could consider using lower-intensity statin combined with bile acid sequestrant or ezetimibe among high-risk patients intolerant of or unresponsive to statins; however, this strategy should be used with caution given the lack of evidence on long-term clinical benefits and harms,” they wrote.