2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk

New data from the FOURIER and the SPIRE-1 and -2 studies with PCSK9 inhibitors led to an update of the 2016 ACC consensus paper on the role of non-statin therapies for LDL-C lowering in the management of atherosclerotic CV disease (ASCVD) risk. The aim of the update is to answer the following questions regarding the use of non-statin therapies:

• In what patient populations should non-statin therapies be considered?
• In what situations should non-statin therapies be considered, that is, when is the amount of LDL-C lowering less than anticipated, less than desired, or inadequate, and which treatment options should be considered in patients who are truly statin intolerant?
• If non-statin therapies are to be added, which agents or therapies should be considered and in what order?

The main changes to the 2016 consensus paper are the following:

• The 2016 consensus thresholds for the evaluation of the net ASCVD risk were the percent reduction in LDL-C or absolute LDL-C levels in patients with clinical ASCVD, in patients with baseline LDL-C ≥ 190 mg/dL, or in patients in primary prevention. In patients with diabetes with or without clinical ASCVD, it was stated that the clinician may consider absolute LDL-C and/or non-HDL-C levels. In the 2017 update, both LDL-C and non-HDL-C thresholds can be used for all patients.
• For patients with clinical ASCVD and baseline LDL-C of 70-189 mg/dL, the threshold for consideration of net ASCVD risk reduction benefit is an LDL-C reduction of at least 50%, LDL-C< 70 mg/dL or non-HDL-C < 100 mg/dL, independently of the existence of comorbidities. In the 2016 consensus paper, these thresholds were recommended only for patients with comorbidities.
• In the 2016 consensus paper, during the decision-making to proceed with the addition of a non-statin therapy on top of a statin, it was deemed reasonable to consider the addition of ezetimibe as the initial agent and a PCSK9 inhibitor as the second agent. In the 2017 update, the choice of the add-on non-statin agent should weigh the addition of either ezetimibe or a PCSK9 inhibitor in light of considerations of the additional percent LDL-C reduction desired, patients’ preferences, costs, route of administration, and other factors.
• In the 2016 consensus paper, the additional factors for the identification of higher-risk patients with clinical ASCVD included diabetes, a recent ASCVD event (<3 months), an ASCVD event while already taking a statin, poorly controlled other major ASCVD risk factors, elevated lipoprotein(a), chronic kidney disease, symptomatic HF, maintenance hemodialysis, and baseline LDL-C of at least 190 mg/dL not due to secondary causes. The 2017 update added being 65 years or older, prior MI or non-hemorrhagic stroke, current daily cigarette smoking, symptomatic PAD with prior MI or stroke, history of non-MI related coronary revascularization, residual CAD with stenosis ≥ 40% in ≥ 2 large vessels, HDL-C< 40 mg/dL for men and < 50 mg/dL for women, hr-CRP > 2 mg/L, or metabolic syndrome.

The 2017 update of the 2016 consensus paper addresses current gaps in care for LDL-C lowering to reduce ASCVD risk. The algorithms endorse the 4 evidence-based statin benefit groups identified in the 2013 ACC/AHA cholesterol guidelines and assume that the patient is currently taking or has attempted to take a statin, given that this is the most effective initial therapy. The 4 evidence-based statin benefit groups are:

• Patients with clinical ASCVD
• Patients with LDL-C ≥190 mg/dL, not due to secondary causes
• Patients aged 40 - 75 years with DM and LDL-C 70 - 189 mg/dL
• Patients aged 40 - 75 years without DM, but with LDL-C 70 - 189 mg/dL and predicted 10-year ASCVD risk ≥7.5%.

Find the full focused update at J Am Coll Cardiol