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A Mendelian randomization analysis study (209) detected that lowering LDL-C and PCSK9 protein levels by PCSK9 variants was relevant to an increase in CB, demonstrating that direct bilirubin is increased with the use of newer lipid-lowering therapies like the preprotein convertase chytokeratase/kexin type 9 (PCSK9), monoclonal antibody inhibitors: alirocumab and evolocumab, and hepatic PCSK9 siRNA inhibitor inclisiran

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However, most of this evidence is still not based on large, high-quality human trials