Nonetheless, in patients with very severe hypercholesterolemia, adding sequestrants to otherwise maximal cholesterol-lowering therapy in patients who are not eligible for a PCSK9 inhib- itor may be considered. 4. PCSK9 inhibitors are promising drugs for treat- ment of FH.S4.2-9,S4.2-13 S4.2-15 Two placebo-con- trolled RCTs of the efficacy and safety of PCSK9 inhibitors in patients with heterozygous FH who were 18 years of age and taking stable, maxi- mally tolerated statin therapy demonstrated favorable safety profiles and an additional 50% reduction in LDL-C.S4.2-10,S4.2-15 There are no cur- rently available outcomes trials of PCSK9 inhibi- tors in patients with ASCVD heterozygous FH. In patients with LDL-C levels 190 mg/dL ( 4.9 mmol/L), advancing age is associated with pro- gressively increasing ASCVD risk,S4.2-4 and age- related risk would likely apply to those with heterozygous FH because of their higher lifetime exposure to increased LDL-C concentration.S4.2-18 A long-term prospective cohort registry study of CLINICAL STATEMENTS AND GUIDELINES 2404 patients with heterozygous FH (molecularly defined) taking contemporary statin with or with- out ezetimibe treatment regimens identified age >30 years, male sex, history of ASCVD, high blood pressure, increased waist circumference, active smoking, Lp(a) 50 mg/dL, and LDL-C levels 100 mg/dL ( 2.6 mmol/L) as independent predictors of incident ASCVD over a 5.5-year follow-up Because other medical interventions that lower LDL-C levels via increased expression of LDL receptors reduce ASCVD risk,S4.2-9 the use of PCSK9 inhibitors in selected maximally treated patients with heterozygous FH with persistently elevated LDL-C levels may be considered after a clinician patient discussion of the net benefits versus the cost of such therapy. 5. 