Update of ACC Expert consensus decision pathway on management of atherosclerotic CVD risk

Data of the FOURIER and SPIRE trials called for an update of the 2016 ACC consensus paper on the role of non-statin therapies for LDL-C-lowering in the management of ASCVD 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