Dyslipidemia

For LDL-C–predominant dyslipidemia, establish whether the patient has clinical ASCVD, diabetes, severe primary hypercholesterolemia, or a primary-prevention risk decision. Statins remain the treatment foundation for secondary prevention because of established efficacy, safety, tolerability, and cost-effectiveness; ASCVD risk reduction rises in graded fashion with the magnitude of LDL-C lowering. jaccjacc2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA ...

Do not interpret an isolated LDL-C value as the complete atherogenic burden when triglycerides are elevated, diabetes is present, or achieved LDL-C is below 70 mg/dL. Order apolipoprotein B in these settings when residual particle-related risk could be underestimated by the standard lipid panel; non-HDL-C is also readily calculated without added cost and reflects all atherogenic cholesterol. jacc+2jacc2026 Dyslipidemia Guideline-at-a-Glance - JACCjaccCholesterol Levels and Cardiovascular Outcomes Following Statin ...jaccImportance and Management of Non–High-Density Lipoprotein ...

Separate severe hypertriglyceridemia from LDL-C treatment escalation. Persistent fasting triglycerides of 500 to 999 mg/dL warrant a pancreatitis-prevention strategy centered on a low-fat diet and consideration of fenofibrate or prescription omega-3 fatty acids. In adults aged 40 to 75 years with ASCVD, diabetes, or 10-year ASCVD risk of at least 5%, simultaneously initiate or intensify statin therapy. ACCACCACC Consensus on ASCVD Risk Reduction in Hypertriglyceridemia

When LDL-C is markedly elevated or response to statin therapy is unexpectedly poor, first evaluate for secondary dyslipidemia before assigning familial hypercholesterolemia. If secondary causes are excluded, assess for LDL receptor pathway disease using Dutch Lipid Clinic Network criteria, Simon Broome criteria, or ACC/AHA diagnostic criteria. ccjmccjmMy adult patient’s hypercholesterolemia is not responding to statins—what’s next? | Cleveland Clinic Journal of medicine

Heterozygous familial hypercholesterolemia typically reflects a mutation affecting one allele, whereas homozygous familial hypercholesterolemia produces substantially more severe disease; LDL-C in heterozygous disease may be two to three times above normal. The distinction changes escalation because lomitapide and evinacumab are specifically considered for homozygous familial hypercholesterolemia. ccjm+1ccjmMy adult patient’s hypercholesterolemia is not responding to statins—what’s next? | Cleveland Clinic Journal of medicineACCStepwise Approach to Novel Lipid-Lowering Medications - American College of Cardiology

Use treatment response as a diagnostic and management discriminator. If a patient requires more than 25% additional LDL-C lowering despite maximally tolerated statin therapy, or has very high risk such as LDL-C greater than 190 mg/dL, PCSK9 inhibition can be initiated before ezetimibe rather than relying on ezetimibe alone, which typically lowers LDL-C by about 25%. ccjmccjmMy adult patient’s hypercholesterolemia is not responding to statins—what’s next? | Cleveland Clinic Journal of medicine

For established ASCVD, maintain maximally tolerated statin therapy before adding nonstatins unless statin-attributed adverse effects preclude use. In very-high-risk ASCVD, add a PCSK9 monoclonal antibody when LDL-C remains at least 70 mg/dL or non-HDL-C remains at least 100 mg/dL despite ezetimibe and maximally tolerated statin therapy. ACCACCStepwise Approach to Novel Lipid-Lowering Medications - American College of Cardiology

For ASCVD not classified as very high risk in patients aged 75 years or younger, add ezetimibe when LDL-C remains at least 70 mg/dL on maximally tolerated statin therapy. If LDL-C remains at least 70 mg/dL despite the statin-ezetimibe combination, consider bempedoic acid; PCSK9 inhibition is appropriate when a larger additional LDL-C reduction is needed. ACCACCStepwise Approach to Novel Lipid-Lowering Medications - American College of Cardiology

In diabetes with statin-attributed adverse effects, ezetimibe, bempedoic acid, and/or a PCSK9 monoclonal antibody are recommended options to lower LDL-C and reduce ASCVD risk. Select among them based on needed LDL-C reduction, injection preference, cost, and ability to sustain adherence. ACCACCLipid Manager - Mobile and Web Apps

Inclisiran is an option when less frequent injections are preferred, but cardiovascular outcome studies in ASCVD are ongoing. Do not equate LDL-C lowering with completed outcomes evidence when choosing between inclisiran and therapies with established cardiovascular benefit, including statins, ezetimibe, PCSK9 monoclonal antibodies, and icosapent ethyl. ACC+1ACCStepwise Approach to Novel Lipid-Lowering Medications - American College of CardiologyACCLipid Manager - Mobile and Web Apps

For persistent fasting triglycerides of 500 to 999 mg/dL in adults aged 20 to 39 years, emphasize a low-fat diet and consider fenofibrate or prescription omega-3 fatty acids to reduce pancreatitis risk. For those aged 40 to 75 years with 10-year ASCVD risk of at least 5%, diabetes, or ASCVD, initiate or intensify statin therapy in addition to a low-fat or very-low-fat diet and consideration of fenofibrate or prescription omega-3 fatty acids. ACCACCACC Consensus on ASCVD Risk Reduction in Hypertriglyceridemia

Prescription omega-3 fatty acid products include EPA/DHA mixtures and purified EPA as icosapent ethyl. At 2 g twice daily, prescription omega-3 fatty acids lower triglycerides by approximately 30%. Low-dose omega-3 formulations have not reduced ASCVD events in primary or secondary prevention trials; cardiovascular event reduction has been shown in trials of EPA alone. ACCACCACC Consensus on ASCVD Risk Reduction in Hypertriglyceridemia

Do not use triglyceride lowering alone as a substitute for LDL-C–directed prevention. In patients with ASCVD risk indications, statin therapy remains central, while fibrates and prescription omega-3 therapy are selected chiefly for severe triglyceride elevation and pancreatitis-risk reduction. jacc+1jacc2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA ...ACCACC Consensus on ASCVD Risk Reduction in Hypertriglyceridemia

Measure Lp(a) at least once in every adult to identify inherited elevation. Lp(a) at or above 125 nmol/L (50 mg/dL) is a risk-enhancing factor associated with about 1.4-fold higher ASCVD risk, and levels at or above 250 nmol/L (100 mg/dL) are associated with at least twofold higher estimated risk; these findings support intensified LDL-C lowering and more aggressive management of modifiable risk factors. jaccjacc2026 Dyslipidemia Guideline-at-a-Glance - JACC

An Lp(a) concentration above 180 mg/dL (430 nmol/L) identifies a very high inherited level with lifetime ASCVD risk comparable to heterozygous familial hypercholesterolemia. Because circulating Lp(a) is largely genetically determined and minimally modified by diet or environmental exposures, use the result for risk stratification and family-oriented clinical assessment rather than expecting lifestyle intervention to normalize it. jacc+1jacc2026 Dyslipidemia Guideline-at-a-Glance - JACCjaccLipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic ...

Consider coronary artery calcium scoring to refine risk and guide LDL-C and non-HDL-C goals in men aged at least 40 years and women aged at least 45 years when primary-prevention treatment intensity remains uncertain. Interpret both absolute calcium burden and the age-, sex-, and race-standardized percentile because each adds prognostic information. jaccjacc2026 Dyslipidemia Guideline-at-a-Glance - JACC

Reassess the lipid panel after therapy changes to determine whether the patient has crossed the escalation threshold relevant to the treatment pathway, such as LDL-C 70 mg/dL or non-HDL-C 100 mg/dL in very-high-risk ASCVD. In patients with elevated triglycerides, diabetes, or low achieved LDL-C, repeat or obtain ApoB when discordance with LDL-C could change residual-risk assessment. jacc+1jacc2026 Dyslipidemia Guideline-at-a-Glance - JACCACCStepwise Approach to Novel Lipid-Lowering Medications - American College of Cardiology