Patients with primary severe hypercholesterolemia (LDL-C 190 mg/dL [ 4.9 mmol/L]) have a high risk of ASCVDS4.3-23 and premature and recurrent coronary events. Although no randomized, pla- cebo-controlled trials of statin therapy have been done exclusively in subjects with LDL-C 190 mg/ dL, a placebo-controlled primary-prevention study performed in men with a mean baseline LDL-C of 192 17 mg/dL demonstrated a reduced inci- dence of MI and cardiovascular death in those receiving pravastatin 40 mg daily.S4.3-24 These find- ings were extended in a post hoc analysis of 2 560 exclusively primary-prevention subjects in that RCT and in a 20-year observational post-trial long-term follow-up study.S4.3-37 Because moder- ate- or high-intensity statins have been shown to reduce ASCVD risk and because high-intensity statins provide greater ASCVD risk reduction than do moderate-intensity statins or placebo,S4.3-2 maximally tolerated statin therapy should be administered to patients with LDL-C 190 mg/dL. Please refer to the 2018 cholesterol guidelineS4.3-1 for recommendations on the use of non-statin therapies in these patients. 5. The occurrence of a first ASCVD event in patients 40 to 75 years of age with diabetes is associated with increased morbidity and mortality compared with those without diabetes, which places a partic- ularly high premium on primary prevention in indi- viduals with diabetes in that age range. Although trials using moderate-intensity statin therapy have demonstrated significant benefit in such indi- viduals, the residual risk in the statin treatment groups in these trials remained high. (eg, 8.5% had major cardiovascular events in 3.8 years).S4.3-13 The benefit from statin therapy is related to both global risk and intensity of treatment,S4.3-2 and no RCTs of high-intensity statin therapy have been carried out in cohorts of patients exclusively with diabetes. 