The FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) evaluated the PCSK9 inhibitor evolocumab among patients with ASCVD who met at least 1 major or 2 minor Recruitment was limited to patients who had LDL-C 70 mg/dL ( 1.8 mmol/L) (or non HDL-C 100 mg/dL ( 2.6 mmol/L)) on maxi- mal statin ezetimibe. At a median follow-up of 2.2 years, evolocumab significantly reduced composite ASCVD (15% RRR; 1.5% AAR) with- out neurocognitive side effects,S4.1-16,S4.1-17 The ODYSSEY OUTCOMES trial (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), tested alirocumab in patients on maximal statin ezetimibe with ACS over a median of 2.8 years, observed a 15% RRR (1.6% Figure 1. Secondary prevention in patients with clinical ASCVD. Colors correspond to Class of Recommendation in Table 2. Clinical ASCVD consists of ACS, those with history of MI, stable or unstable angina or coronary other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin. Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions (Table 4). ACS indicates acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; MI, myocardial infarction; and PCSK9-I, PCSK9 inhibitor. CLINICAL STATEMENTS AND GUIDELINES ARR) in composite ASCVD events.S4.1-18 Together, FOURIER and ODYSSEY OUTCOMES justify a COR of IIa for PCSK9 inhibitors (acknowledging effi- cacy, but at the same time recognizing that there is limited experience with long-term tolerance of expensive monoclonal antibodies that is also inconvenient because it requires repetitive admin- istration via the parenteral route). 