The following are key points to remember about the 2017 Focused Update of the 2016 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for Low-Density Lipoprotein (LDL)-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease (ASCVD) Risk:

1. At the time of the 2013 ACC/AHA Cholesterol guidelines, the panel found no supporting evidence for the routine use of non-statin drugs in combination with statins for the reduction of ASCVD events. Three years later, the ACC published its first expert consensus decision pathway related to the role of non-statin therapies for LDL-cholesterol lowering. Since then, additional evidence, in particular related proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, has been published. The revised recommendations (published in September 2017) pertain to patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention.
2. The writing committee did not provide new or revised recommendations related to primary prevention groups (patients with LDL-C <190 mg/dl with or without diabetes or patients without ASCVD and an LDL ≥190 mg/dl) in regards to the use of PCSK9 inhibitors or ezetimibe.
3. Thresholds for consideration of ASCVD risk reduction are percent reduction in LDL (current LDL compared to baseline LDL). Absolute LDL or non–high-density lipoprotein (HDL) levels may be considered for each of the four statin benefit groups. The groups are: 1) adults with clinical ASCVD; 2) adults with an LDL ≥190 mg/dl; 3) adults ages 40-75 years without ASCVD with diabetes mellitus (DM) and an LDL between 70 and 189 mg/dl; and 4) adults between ages 40 and 75 years without ASCVD or DM, with an LDL between 70 and 189 mg/dl, and an estimated 10-year risk for ASCVD of ≥7.5% (using the pooled risk equation). Consideration of non-statin therapies to provide adequate percent LDL lowering was based on evidence from two trials: 1) FOURIER, which included patients with clinical ASCVD with or without DM; and SPIRE-2, which included high-risk primary prevention patients and patients with familial hypercholesterolemia.
4. Percent risk reduction for patients with clinical ASCVD, with or without comorbidities, is recommended to be ≥50% for all patients with clinical ASCVD and a baseline LDL level. Consideration for an LDL <70 mg/dl or a non-HDL >100 mg/dl can be given as well. The recommendations to consider non-statin therapies to all patients with clinical ASCVD are based on evidence from FOURIER and IMPROVE-IT trials.
5. Addition of non-statin therapies to maximally tolerated statin therapy is recommended to be considered among patients with clinical ASCVD when additional LDL lowering is desired. Addition of either ezetimibe or a PCSK9 inhibitor should also factor in patient preferences, costs, and route of administration in addition to percent of LDL lowering desired. For <25% of additional LDL lowering, ezetimibe may be preferred, while in patients who require >25% additional LDL lower, a PCSK9 inhibitor may be preferred. Periodic measurement of lipids (to determine adherence and response to therapy) continues to be recommended including at the start of treatment, 4-12 weeks after initiation of a statin, and thereafter every 3-12 months as clinically indicated. The writing committee recommended monitoring lipids at 4-12 weeks after modification to LDL-lowering therapy, including the addition of a non-statin therapy.

Keywords: Atherosclerosis, Cardiovascular Diseases, Cholesterol, Cholesterol, LDL, Consensus, Decision Making, Diabetes Mellitus, Dyslipidemias, Genetic Diseases, Inborn, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Life Style, Lipids, Lipid Metabolism, Inborn Errors, Lipoproteins, Patient Compliance, Primary Prevention, Proprotein Convertases, Risk Assessment, Risk Factors, Risk Reduction Behavior, Secondary Prevention, Subtilisins

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