2022 ACC Expert Consensus on ASCVD Management

Non-statin therapies for LDL-C lowering in management of ASCVD risk: 2022 ACC expert consensus.

Key Takeaway

The ACC convened a writing committee to provide guidance for implementation of newer non-statin therapies for LDL-C lowering in the management of ASCVD risk, which recommended that, while proceeding with the addition of non-statin therapy to maximally tolerated statin therapy, the following should be considered^*:

• In adults with ASCVD not at VHR (threshold LDL-C <55 mg/dL and ≥50% LDL-C reduction)
  • Addition of ezetimibe and/or PCSK9 mAb
  • For additional LDL-C lowering, bempedoic acid or inclisiran may be considered
• In adults with ASCVD not at VHR (threshold LDL-C <70 mg/dL and ≥50% LDL-C reduction)
  • Addition of ezetimibe
  • For additional LDL-C lowering, may consider adding/replacing with PCSK9 mAb
  • Thereafter lowering with bempedoic acid or inclisiran may be considered
• In adults with clinical ASCVD and baseline LDL-C ≥190 mg/dL (threshold LDL-C <70 mg/dL and ≥50% LDL-C reduction)
  • Addition of ezetimibe and/or PCSK9 mAb
  • For additional LDL-C lowering, may consider bempedoic acid/inclisiran
  • Thereafter may consider LDL apheresis under care of lipid specialist
• In adults with clinical ASCVD, at VHR and baseline LDL-C ≥190 mg/dL (threshold LDL-C <55 mg/dL and ≥50% LDL-C reduction)
  • Addition of ezetimibe and/or PCSK9 mAb
  • For additional LDL-C lowering, may consider bempedoic acid/inclisiran
  • Thereafter lowering with evinacumab, lomitapide and/or LDL apheresis
• In adults with possible statin associated side effects (SASE)
  • Consider PCSK9 mAb and/or ezetimibe
  • For additional LDL-C lowering, bempedoic acid/inclisiran
  • Thereafter lowering with evinacumab for HoFH
• Simultaneous addition of 2 agents may be considered for more rapid risk reduction of recurrent events, in some adults from above categories requiring greater LDL-C reduction than any therapy alone can expect to achieve.
• Maximally tolerated statin therapy with/without ezetimibe and PCSK9 mAb, or maximally tolerated statin therapy and ezetimibe can be considered.

Why this matters

Since publication of the 2018 AHA/ACC/ multisociety cholesterol guideline, several newer non-statin agents have demonstrated LDL-C lowering efficacy, received approval, and been made available for management of at-risk patients.

• However, this led to gaps in expert guidance with reference to the role of available non-statin therapies.

The ACC convened a writing committee, in 2021 to address current gaps in care for LDL-C lowering to reduce ASCVD risk and to provide further recommendations regarding use of newer non-statin therapies.

• This was extensively based on the evidence provided by the 2013 ACC/AHA and 2018 AHA/ACC/multisociety cholesterol guidelines.

Guidance was provided to answer the questions regarding the use of non-statin therapies with reference to patient populations, situations, and type of newer non-statin therapies to be considered.

Study Design

The solution set oversight committee provided algorithms endorsing 4 evidence-based patient management groups identified in the guidelines and assumed the patients to be taking or having attempted to take maximally tolerated dose of statin and trying to determine the need for additional therapy to further reduce ASCVD risk:

• Adults (≥20 years) with clinical ASCVD on statin therapy for secondary prevention
• Adults (≥20 years) with LDL-C ≥190 mg/dL on statin therapy for primary prevention
• Adults (45–70 years) without ASCVD but with diabetes LDL-C <190 mg/dL on statin therapy for primary prevention
• Adults (45–70 years) without ASCVD or diabetes LDL-C 70–189 mg/dL and an estimated 10-year risk for ASCVD ≥7.5%, on statin therapy for primary prevention

The recommendation process did not involve formal systematic reviews, grading of evidence, or synthesis of evidence.

Key Highlights

The ACC provided practical guidance for clinicians and patients in situations not covered by the 2018 AHA/ACC/multisociety cholesterol guideline until a formal review of scientific evidence and cardiovascular outcomes trials of newer agents for ASCVD risk reduction was completed.

Guidance for adults with clinical ASCVD on statin therapy for secondary prevention

Considerations that may favor the initial choice of non-statin agent

Guidance for adults with possible sase

For additional details, please refer to the source publication Lloyd-Jones DM, et al.
To get SI units from mg/dL to mmol/L multiply by 0.02586.
^*From figures 2A–D and figure 7 of source publication Lloyd-Jones DM, et al.
^† Key limitations for all 4 study groups

Limitations

• Suggested non-statin therapies had not been well studied in the patient population.
• Generalizability of the recommendations provided for the use of all statin add-on therapies for ethnic minorities was uncertain.
• Detailed recommendations for other special populations of patients with specific comorbidities/conditions were not provided.