Severe Hypercholesterolemia (LDL-C 190 mg/dL [ 4.9 mmol/L]) Recommendations for Primary Severe Hypercholesterolemia (LDL-C 190 mg/dL [ 4.9 mmol/L]) Referenced studies that support recommendations are summarized in Online Data Supplements 9 and 10. COR LOE Recommendations I B-R In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL or higher ( 4.9 mmol/L), maximally tolerated statin therapy IIa B-R In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL or higher ( 4.9 mmol/L) who achieve less than a 50% reduction in LDL-C while receiving maximally tolerated statin therapy and/ or have an LDL-C level of 100 mg/dL or higher ( 2.6 mmol/L), ezetimibe therapy is IIb B-R In patients 20 to 75 years of age with a baseline LDL-C level of 190 mg/dL or higher ( 4.9 mmol/L), who achieve less than a 50% reduction in LDL-C levels and have fasting triglycerides 300 mg/dL or lower ( 3.4 mmol/L), while taking maximally tolerated statin and ezetimibe therapy, the addition of a bile acid sequestrant may be IIb B-R In patients 30 to 75 years of age with heterozygous FH and with an LDL-C level of 100 mg/dL or higher ( 2.6 mmol/L) while taking maximally tolerated statin and ezetimibe therapy, the addition of a PCSK9 inhibitor may be considered.S4.2-9,S4.2-13 S4.2-15 IIb C-LD In patients 40 to 75 years of age with a baseline LDL-C level of 220 mg/dL or higher ( 5.7 mmol/L) and who achieve an on-treatment LDL-C level of 130 mg/ dL or higher ( 3.4 mmol/L) while receiving maximally tolerated statin and ezetimibe therapy, the addition of a PCSK9 inhibitor may be considered.S4.2-13 S4.2-17 Value Statement: Uncertain Value (B-NR) Among patients with FH without evidence of clinical ASCVD taking maximally tolerated statin and ezetimibe therapy, PCSK9 inhibitors provide uncertain value at mid- 2018 US list prices. 