PCSK9 and atherosclerosis: PCSK9 directed therapies, either mAbs or siRNA should be used to further lower LDL-C in those at higher risk (previous ASCVD, elevated subclinical coronary atherosclerosis plaque burden, those with multiple risk factors like smoking, diabetes, hypertension, low HDL-C, high lipoprotein(a) among others) or who persist with LDL-C levels above recommended goals [29, 43].