The ACC developed the 2022 ACC Expert Consensus Decision Pathway† (2022 Consensus Pathway) to address gaps in care for LDL-C lowering to reduce ASCVD risk. It relies on evidence established by the 2013 ACC/AHA and 2018 AHA/ACC/Multisociety cholesterol guidelines and provides further recommendations regarding the use of non-statin therapies.
Use the chart below as a guide for suggested treatment options for your patients with high LDL-C and when a ≥50% reduction in LDL-C is needed1
If still not achieved…
If still not achieved…
If still not achieved…
Consider the below drug therapy options or referral to lipid specialists:
*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
Contraindications: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse Reactions in Primary Hyperlipidemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
Adverse Reactions in the Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.
Repatha® is indicated: