Synopsis Clinical ASCVD encompasses ACS, those with history of MI, stable or unstable angina or coronary or other arterial revascularization, stroke, TIA or PAD including aortic aneurysm, all of atherosclerotic origin. The writ- ing group used primarily the Cholesterol Treatment Tri- alists (CTT) meta-analysisS4.1-3,S4.1-4 of statin RCTs plus Additional RCTs have used nonstatin drugs as add-ons to statin therapy and are included here. As a primary recommendation, high- intensity statin therapy is indicated for clinical ASCVD, but if this cannot be used, moderate-intensity statin therapy can be initiated (Figure 1). The first goal is to achieve a 50% reduction in LDL-C levels, but if LDL-C levels remains 70 mg/dL ( 1.8 mmol/L) on maximally tolerated statin therapy, adding ezetimibe may be rea- sonable. In patients >75 years of age with ASCVD, po- tential benefits versus adverse effects of statin therapy should be considered before initiation of statin therapy. Finally, in very high-risk patients with multiple high-risk clinical factors, ezetimibe can be added to maximally tolerated statin therapy. Furthermore, if LDL-C levels remain 70 mg/dL ( 1.8 mmol/L), adding a PCSK9 in- hibitor is reasonable if the cost/benefit ratio is favor- able. In patients with HF due to ischemic heart disease, moderate-intensity statins may be considered. Recommendation-Specific Supportive Text showed that LDL-C lowering with statins reduces major ASCVD events. Patients with strokeS4.1-1 or peripheral also derive these benefits. In a meta-analysis of 5 RCTs,S4.1-3 high-intensity statins compared with moderate-intensity statin therapy, significantly reduced major vascular events by 15% with no significant reduction in coronary deaths. Large absolute LDL-C reduction was associated with a larger proportional reduc- tion in major vascular events.S4.1-4 High-intensity statin therapy generally reduces LDL-C levels by 50%. This percentage can be used to judge clinical efficacy. 