*2022 ACC Expert Consensus Decision Pathway on the role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee | Journal of the American College of Cardiology.¹

^†Note that this process did not involve formal systematic reviews, grading of evidence, or synthesis of evidence. The goal was to provide practical guidance in situations not covered by the 2018 AHA/ACC/Multisociety cholesterol guideline until the next round of guidelines has the opportunity to formally review recent scientific evidence.

^‡A retrospective cohort study of 16,344 patients 19 years of age or older with a history of a major ASCVD event using data from MarketScan database. LDL-C values were available through linkage with the quest diagnostics laboratory database between January 1, 2015 and January 1, 2016. Patients were followed from January 1, 2016 through December 31, 2017, for recurrent ASCVD events. Major ASCVD events included a recent ACS, history of MI other than a recent ACS, history of ischemic stroke, and symptomatic PAD.

^§Non-statin pharmacologic options are considered after optimizing lifestyle, controlling ASCVD risk factors, adhering to guideline-recommended statin therapy (and increasing to high-intensity statin if not already taking), and evaluating for statin intolerance.

^**Includes age ≥65 years, hypertension, diabetes, heterozygous familial hypercholesterolemia, history of prior coronary artery bypass surgery, or percutaneous coronary intervention.¹

^††Strongly consider PCSK9i mAbs if fully statin intolerant and attempts to lower LDL-C with ezetimibe or bile acid sequestrants result in persistent <50% LDL-C reduction (or may consider if LDL ≥70 mg/dL or non–HDL-C ≥100 mg/dL). Consider PCSK9i mAbs only if on maximally tolerated statin therapy (and either ezetimibe or bile acid sequestrants if not very high-risk ASCVD), with persistent <50% LDL-C reduction (or may consider if LDL-C ≥70 mg/dL or non–HDL-C ≥100 mg/dL). No cardiovascular outcome studies exist for bempedoic acid or inclisiran.¹

^‡‡PCSK9i mAbs may be preferred by the 2022 ACC Consensus Pathway as the initial non-statin agent in patients who require >25% additional lowering of LDL-C or based on clinical-patient decision-making. Potential considerations in use of PCSK9i mAbs, compared to ezetimibe, include net risk reduction benefits of a PCSK9i mAbs, administration through subcutaneous injection, every 2 weeks or once monthly dosing schedule, storage requirements, and cost.¹