Ezetimibe use before PCSK9 inhibitor is recom- mended because ezetimibe is available as a generic drug and has proven safety.211 This approach is supported by 2 simulation studies from large popu- lations of very high-risk patients showing that ezeti- mibe plus statin therapy lowers LDL-C to <70 mg/ dL (1.8 mmol/L) in most patients, leaving a minority eligible for a PCSK9 inhibitor.217,218 In addition, the TST trial of patients with ischemic stroke used ezeti- mibe as second-line therapy to achieve the LDL-C Table 5. Very High Risk of Future ASCVD Events Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions: Major ASCVD events History of ischemic stroke Recent acute coronary syndrome (within the past 12 mo) History of MI (other than recent ACS event listed above) Symptomatic peripheral arterial disease (history of claudication with ankle-brachial index <0.85 or previous revascularization or amputation High-risk conditions Age 65 y Heterozygous familial hypercholesterolemia History of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events Diabetes Hypertension Chronic kidney disease (estimated glomerular filtration rate, 15 59 ) Current smoking The information in this table is from the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol.31 For high-intensity statin therapy, the guide- line recommends atorvastatin 80 mg daily or rosuvastatin 20 mg daily. Please refer to the guideline for contraindications to high-intensity statin therapy and recommendations for moderate-intensity statin therapy. ACS indicates acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; and MI, myocardial infarction. CLINICAL STATEMENTS AND GUIDELINES Kleindorfer supporting the use of ezetimibe before PCSK-9 inhibitors in patients with ischemic stroke who are not at their LDL-C targets. 4. 