Patients with primary severe hypercholesterolemia (LDL-C levels 190 mg/dL [ 4.9 mmol/L]) have a high-risk of ASCVDS4.2-2,S4.2-4,S4.2-18 and premature and recurrent coronary events.S4.2-3 Although there have been no randomized, placebo-controlled tri- als of statin therapy done exclusively in subjects with LDL-C levels 190 mg/dL ( 4.9 mmol/L), a placebo-controlled primary prevention study performed in men with a mean baseline LDL-C level of 192 17 mg/dL (4.9 0.4 mmol/L) demon- strated a reduced incidence of MI and cardiovas- cular death in those receiving pravastatin 40 mg These findings were extended in a post hoc analysis of 2560 exclusively primary-preven- tion subjects in that RCT and in a 20-year observa- tional post-trial long-term follow-up study.S4.2-19 In addition, retrospective cohort studies have dem- onstrated that statin therapy reduces risk of inci- and of CHD and all-cause deathS4.2-1 in patients with phenotypic or genetically con- firmed FH. Because moderate- or high-intensity statins have been shown to reduce ASCVD risk in both primary- and secondary-prevention trials and because high-intensity statins provide greater ASCVD risk reduction than moderate-intensity statins or placebo,S4.2-7 maximally tolerated statin therapy should be administered to patients with primary severe hypercholesterolemia. 2. A large placebo-controlled RCT examined the effect of simvastatin 80 mg daily, with or without ezetimibe 10 mg daily, on carotid intima-media thickness and plasma lipoproteins over 2 years. Mean LDL-C reduction was greater in the com- bined-therapy group, but there was no difference in carotid intima-media thickness between the 2 groups. 