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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168 August 29, 2023 Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline be guided by the need for continued nitrate therapy versus other alternative options available to the treating clinician. 4.2.6 Lipid Management Recommendations for Lipid Management Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations 1 A 1 In patients with CCD, high-intensity statin ther- apy is recommended with the aim of achieving a ≥50% reduction in LDL-C levels to reduce the risk of MACE.*1–3 1 A 2 In patients in whom high-intensity statin therapy is contraindicated or not tolerated, moderate-intensity statin therapy is recommended with the aim of achieving a 30% to 49% reduction in LDL-C levels to reduce the risk of MACE.*2,4–8 1 A 3 In patients with CCD, adherence to changes in lifestyle and effects of lipid-lowering medication should be assessed by measurement of fasting lipids in 4 to 12 weeks after statin initiation or dose adjustment and then every 3 to 12 months thereafter based on need to assess response or adherence to therapy.*2,9–11 Cost Value Statement: High Value B-NR 4 In patients with CCD, the use of generic formulations of maximally tolerated statin therapy is projected to be cost saving.12,13 2a B-R 5 In patients with CCD who are judged to be at very high risk (Table 10) and on maximally tolerated statin therapy with an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), ezetimibe can be beneficial to further reduce the risk of MACE.*14–19 Cost Value Statement: High Value B-NR 6 In patients with CCD, addition of generic ezetimibe to maximally tolerated statin therapy in appropriately selected patients is projected to be of high economic value at US prices.12,20,21 2a A 7 In patients with CCD who are judged to be at very high risk (Table 10) and who have an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), or a non–high-density lipoprotein cholesterol (HDL-C) level ≥100 mg/dL (≥2.6 mmol/L), on maximally tolerated statin and ezetimibe, a PCSK9 monoclonal antibody can be beneficial to further reduce the risk of MACE.*22–29 Cost Value Statement: Uncertain B-NR 8. In patients with CCD who are very high risk, the use of PCSK9 monoclonal antibodies is projected to be of uncertain economic value at US prices12,20,21,30,31 2b B-R 9 In patients with CCD on maximally tolerated statin therapy with an LDL-C level <100 mg/ dL (<2.6 mmol/L) and a persistent fasting triglyceride level of 150 to 499 mg/dL (1.7–5.6 mmol/L) after addressing secondary causes, icosapent ethyl may be considered to further reduce the risk of MACE and cardiovascular death.32 2b B-R 10 In patients with CCD who are not at very high risk and on maximally tolerated statin therapy with an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), it may be reasonable to add ezetimibe to further reduce the risk of MACE.*14,15,18,19 2b B-R 11 In patients with CCD on maximally tolerated statin therapy who have an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), and in whom ezetimibe and PCSK9 monoclonal antibody are deemed insufficient or not tolerated, it may be reasonable to add bempedoic acid33,34 or inclisiran35 (in place of PCSK9 monoclonal antibody) to further reduce LDL-C levels. 3: No Benefit B-R 12. In patients with CCD receiving statin therapy, adding niacin,36,37 or fenofibrate38 or dietary supplements containing omega-3 fatty acids, are not beneficial in reducing cardiovascular risk.39–41 *Modified from the 2018 AHA/ACC/Multisociety Guideline on the Management of Blood Cholesterol.42 Synopsis LDL-C is a primary cause of atherosclerotic disease and target of lipid management.38 RCTs established the efficacy and safety of high-intensity statin therapy as the preferred initial approach to reduce LDL-C levels by ≥50% and reduce cardiovascular morbidity and mortality rates (Figure 8).1–3 Despite maximally tolerated statin therapy, residual cardiovascular risk persists, especially among patients with CCD and additional high-risk clinical factors (Table 10).14–17 Several nonstatins36–38 did not provide benefit when added to background statin therapy; however, ezetimibe, PCSK9 monoclonal antibodies, and icosapent ethyl further reduce cardiovascular risk when added to background statin therapy.15,22,23,32 Bempedoic acid and inclisiran have only recently become available and, although they effectively reduce LDL-C levels,34,35 RCTs are ongoing to determine their effect on MACE. Clinicians should prioritize use of ezetimibe and PCSK9 monoclonal antibodies when additional LDL-C lowering is necessary in patients on maximally tolerated statin therapy unless not tolerated or effective in achieving desired LDL-C levels. Regardless of the lipid-lowering regimen, lipid monitoring is essential to assess individual response to lipid-lowering therapy and monitor adherence and persistence with therapy over time.9–11 Recommendation-Specific Supportive Text 1 The CTT (Cholesterol Treatment Trialists) meta- analysis of 5 RCTs showed that LDL-C lowering with high-intensity statins compared with moderate-intensity statins reduces major vascular events by 15% (Table 11).2 This benefit occurred irrespective of age, even among patients >75 years of age with established ASCVD.2,3 Greater absolute reductions in LDL-C were associated with a greater proportional reduction in MACE. The greatest absolute benefit from statin therapy Recommendations for Lipid Management (Continued ) COR LOE Recommendations Downloaded from http://ahajournals.org by on October 7, 2026