Lower-dose statins plus combination therapies may be an alternative for patients intolerant of or unresponsive to high-dose statins

Clinicians could cautiously consider using a lower-intensity statin combined with a bile acid sequestrant or ezetimibe for high-risk patients intolerant of or unresponsive to statins, a meta-analysis found.

To compare the clinical benefits, adherence, and harms of lower-intensity statin combination therapy and higher-intensity statin monotherapy among adults at high risk for atherosclerotic cardiovascular disease, researchers conducted a meta-analysis of 36 randomized, controlled trials.

Results appeared online first Feb. 11 at Annals of Internal Medicine.

Combination therapy with bile acid sequestrants or ezetimibe decreased LDL cholesterol at least as well as higher-intensity monotherapy and 0% to 14% more than mid-intensity monotherapy. Compared to high-intensity monotherapy, a mid-intensity statin plus ezetimibe decreased LDL cholesterol 5% to 15% in patients with atherosclerotic cardiovascular disease and 3% to 21% in patients with diabetes.

There were inconsistent effects on lowering LDL cholesterol with a low-intensity statin combined with niacin compared to mid-intensity statin monotherapy, and no studies looked at ω-3 fatty acids, the analysis reported. There was not enough evidence to determine long-term clinical outcomes, adherence or potential harms for all regimens.

The authors noted that high-dose statin regimens have been linked to a statistically significant increased risk for adverse events and resulting nonadherence to therapy. For example, statin users have a 50% greater adjusted odds of musculoskeletal pain than nonusers. One study found that 4% of patients do not respond and another 10% have inadequate LDL cholesterol reduction. Given that statin intolerance and unresponsiveness are relatively common, many clinicians will probably care for such patients at some point, the authors said. However, the combination strategy should be used with caution given the lack of evidence on long-term clinical benefits and harms.

“When considering combination therapy with a lower-intensity statin and bile acid sequestrant, patients may benefit from counseling on separating drug administration to ensure maximal effect of each medication,” the study noted.