In young adults 20 to 39 years of age, an assessment of lifetime risk facilitates the clinician patient risk discussion (see No. 6) and emphasizes intensive lifestyle efforts. In all age groups, lifestyle therapy is the primary interven- tion for metabolic syndrome. 2. In patients with clinical ASCVD, reduce low- density lipoprotein cholesterol (LDL-C) with high-intensity statin therapy or maximally tolerated statin therapy. The more LDL-C is reduced on statin therapy, the greater will be sub- sequent risk reduction. Use a maximally tolerated statin to lower LDL-C levels by 50%. 3. In very high-risk ASCVD, use a LDL-C thresh- old of 70 mg/dL (1.8 mmol/L) to consider addition of nonstatins to statin therapy. Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. In very high-risk ASCVD patients, it is reasonable to add ezetimibe to maximally tolerated statin therapy when the LDL-C level remains 70 mg/dL ( 1.8 mmol/L). In patients at very high risk whose LDL-C level CLINICAL STATEMENTS AND GUIDELINES remains 70 mg/dL ( 1.8 mmol/L) on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable, although the long- term safety (>3 years) is uncertain and cost effec- tiveness is low at mid-2018 list prices. 4. In patients with severe primary hyper- cholesterolemia (LDL-C level 190 mg/dL [ 4.9 mmol/L]), without calculating 10-year ASCVD risk, begin high-intensity statin ther- apy. If the LDL-C level remains 100 mg/dL ( 2.6 mmol/L), adding ezetimibe is reasonable. If the LDL-C level on statin plus ezetimibe remains 100 mg/dL ( 2.6 mmol/L) and the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considered, although the long-term safety (>3 years) is uncer- tain and economic value is uncertain at mid-2018 list prices. 5. 