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. The study was not powered to examine the risk of ASCVD events.S4.2-10 However, a very large placebo-controlled RCT examining ASCVD outcomes in post-ACS patients, performed over a period of 7 years, showed that the addition of ezetimibe 10 mg to simvastatin 40 mg daily resulted in greater ASCVD risk reduction than that produced by statin monotherapy.S4.2-8 Secondary- prevention patients with certain ASCVD risk indi- cators exhibit greater ASCVD risk reduction from ezetimibe therapy than do patients without these Patients with severe hyper- cholesterolemia who are adherent to statins, achieve <50% reduction in LDL-C levels with maximally tolerated statin therapy, and have an LDL-C level 100 mg/dL ( 2.6 mmol/L) are likely to derive additional ASCVD risk reduction from ezetimibe add-on therapy through additional 3. When administered to patients with severe hyper- cholesterolemia who are taking maximally toler- ated statins with or without ezetimibe, bile acid sequestrants have demonstrated LDL-C-lowering However, the clinical utility of bile acid sequestrants is limited by the absence of ASCVD outcomes data when used in combi- nation with statins, as well as by the issues of twice-daily dosing, high pill burden, the absence of well-tolerated generic formulations, drug inter- actions, and the potential for triglyceride eleva- tion. 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. 