To the EDITOR: The CLEAR Outcomes trial showed that in patients with high cardiovascular risk who are unwilling or unable to take statins, bempedoic acid is an effective alternative. Consideration of whether this medication improves outcomes and adds value as compared with alternatives such as ezetimibe is important. Trials of ezetimibe1,2 showed smaller cardiovascular benefits than those in the CLEAR Outcomes trial but used placebo instead of drug comparators in patients taking statins. Conclusions that are drawn from indirect comparisons and dissimilar patient populations may be misleading. The pleotropic effects unique to statins and bempedoic acid may be reason to question whether lowering of the low-density lipoprotein (LDL) cholesterol level alone with ezetimibe or other agents would be equally effective. However, the liver-specific activity of bempedoic acid may limit potential off-target effects beyond lowering of the LDL cholesterol level. Ezetimibe has established outcomes data available, has a good side-effect profile, and is more affordable than bempedoic acid. Comparative effectiveness trials evaluating statin alternatives such as ezetimibe are needed to advance practice and provide cost-effective care for patients who are unwilling or unable to take statins.
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