Atherosclerosis

Treat coronary artery disease, atherothrombotic brain infarction, and peripheral artery disease as clinical ASCVD rather than as risk-factor-only disease. These phenotypes carry secondary-event risk and support intensive LDL-C lowering with a statin, with ezetimibe or PCSK9 inhibition when further reduction is required. PubMedPubMedLipid Management for Secondary Prevention in Atherosclerotic ...

For patients without clinical ASCVD, begin with formal cardiovascular risk assessment and a clinician-patient treatment discussion. When risk remains uncertain after 10-year risk assessment, coronary artery calcium (CAC) can reclassify risk and determine whether lipid-lowering therapy should be initiated or deferred. jacc+1jaccA Critical Appraisal of Lipid Management in the Post-Statin Era - JACCScienceDirectAtherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement

Document the vascular distribution of disease because atherosclerosis is systemic and may involve coronary, cerebrovascular, and peripheral arterial beds. PAD in particular should trigger secondary-prevention lipid management rather than management based only on calculated primary-prevention risk. AHA Journals+2AHA JournalsParsing Atherosclerosis | Circulationjacc2026 ACC/AHA Clinical Performance and Quality Measures for Patients With Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Performance MeasuresScienceDirectCarotid Atherosclerosis - an overview | ScienceDirect Topics

A CAC score of 0 supports deferring statin therapy in selected patients, but not in those with diabetes, LDL-C at least 190 mg/dL, current smoking, or a family history of premature cardiovascular disease. If statin therapy is deferred after CAC 0, repeat CAC in 3 to 5 years. jaccjaccA Critical Appraisal of Lipid Management in the Post-Statin Era - JACC

For CAC 1 to 99 Agatston units and below the 75th percentile, consider a moderate-intensity statin and an LDL-C target below 100 mg/dL; escalation to high-intensity therapy may be appropriate. jaccjaccA Critical Appraisal of Lipid Management in the Post-Statin Era - JACC

For CAC at least 100 Agatston units or at least the 75th percentile, consider moderate- or high-intensity statin therapy with LDL-C below 70 mg/dL; ezetimibe can be considered. CAC at least 1,000 identifies a particularly high plaque burden for which at least 50% LDL-C reduction and LDL-C below 70 mg/dL are proposed, with consideration of high-intensity statin, ezetimibe, and PCSK9 inhibition. jaccjaccA Critical Appraisal of Lipid Management in the Post-Statin Era - JACC

LDL-C is a causal factor in atherosclerotic cardiovascular disease, and randomized-trial evidence links LDL-C reduction to proportional reductions in cardiovascular events. In PAD, high-intensity statin therapy is indicated with an intended LDL-C reduction of at least 50%. jacc+1jacc2026 ACC/AHA Clinical Performance and Quality Measures for Patients With Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Performance MeasuresPubMedLDL-Cholesterol-Lowering Therapy - Prevention and Treatment of Atherosclerosis - NCBI Bookshelf

Recheck LDL-C after establishing maximally tolerated statin therapy. In PAD, LDL-C at least 70 mg/dL despite maximally tolerated statin is the threshold at which adding ezetimibe is reasonable; adding a PCSK9 inhibitor is also reasonable. jaccjacc2026 ACC/AHA Clinical Performance and Quality Measures for Patients With Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Performance Measures

Ezetimibe is the preferred first add-on in older ACC nonstatin guidance because of safety and tolerability. If LDL-C goals remain unmet on maximally tolerated statin plus ezetimibe, a PCSK9 inhibitor can be added; bile acid sequestrants are a second-line option when ezetimibe is not tolerated and triglycerides are not elevated. ccjmccjmPCSK9 inhibition: A promise fulfilled? | Cleveland Clinic Journal of medicine

For patients qualifying for PCSK9 monoclonal antibody therapy, FDA-labeled regimens cited for alirocumab are 75 mg subcutaneously every 2 weeks, with uptitration to 150 mg every 2 weeks; evolocumab is 140 mg subcutaneously every 2 weeks or 420 mg every 4 weeks. Both are indicated with statins for heterozygous familial hypercholesterolemia or known ASCVD requiring further LDL-C reduction despite lifestyle intervention and maximally tolerated statin therapy. ccjmccjmPCSK9 inhibition: A promise fulfilled? | Cleveland Clinic Journal of medicine

Document diabetes, elevated blood pressure, smoking, overweight status, dietary factors, physical inactivity, and inadequate sleep because each is associated with ASCVD risk and can identify a high-risk primary-prevention phenotype when combined with subclinical plaque. ScienceDirectScienceDirectIdentification and management of patients at high-risk for ...

Measure and act on the full atherogenic-risk context in younger adults rather than relying exclusively on short-term event prediction. Apolipoprotein B and lipoprotein(a) can inform long-term ASCVD risk, while CAC and polygenic risk scores have potential utility but uncertain optimal use in this population. ScienceDirectScienceDirectManaging Atherosclerotic Cardiovascular Risk in Young Adults

An elevated lipoprotein(a) concentration can substantially increase estimated lifetime ASCVD risk; specific highly effective messenger RNA-targeted Lp(a)-lowering therapies remain in clinical development. Use the result to intensify management of modifiable risk factors and LDL-C rather than waiting for an Lp(a)-specific drug. ScienceDirectScienceDirectManaging Atherosclerotic Cardiovascular Risk in Young Adults

Monitor LDL-C to establish whether statin therapy produces the intended response and whether the LDL-C threshold for add-on therapy has been reached. In PAD, an LDL-C value at least 70 mg/dL on maximally tolerated statin should prompt a documented choice between adding ezetimibe and adding a PCSK9 inhibitor. jaccjacc2026 ACC/AHA Clinical Performance and Quality Measures for Patients With Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Performance Measures

Do not use serial coronary CT angiography as a routine surrogate for treatment success. In PARADIGM, statin use was associated with lower risk of annualized total plaque-volume increase above the cohort median, but was not associated with progression to at least 50% diameter stenosis on follow-up coronary CT angiography. jaccjaccEffects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study

For a patient in whom CAC 0 led to statin deferral, repeat CAC after 3 to 5 years. Otherwise, repeat imaging should be driven by a new clinical question rather than by a desire to document plaque regression. jacc+1jaccA Critical Appraisal of Lipid Management in the Post-Statin Era - JACCjaccEffects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study