American College of Cardiology, American Heart Association Update Guidelines for the Management of Dyslipidemia

The 2026 American College of Cardiology/American Heart Association Guideline on the management of dyslipidemia officially retired and replaced the 2018 cholesterol recommendations, introducing a more comprehensive framework for clinicians and pharmacists to assess and treat atherosclerotic cardiovascular disease (ASCVD) risk. Endorsed by organizations including the American Pharmacists Association, these guidelines serve as a comprehensive guideline that prioritizes earlier intervention through lifestyle optimization and lower treatment targets for those at highest risk.^1,2

“We know 80% or more of cardiovascular disease is preventable, and elevated LDL cholesterol, sometimes referred to as ‘bad’ cholesterol, is a major part of that risk,” Roger Blumenthal, MD, FACC, FAHA, chair of the guideline writing committee and director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, said in a news release.² “While we want to try to optimize healthy lifestyle habits as the first step to lower cholesterol, we realize that if lipid numbers aren’t within the desirable range after a period of lifestyle optimization, we should consider adding lipid-lowering medication earlier than we would have considered 10 years ago.”

A fundamental shift in the new guidance is the adoption of the Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations, which replace the older Pooled Cohort Equations to provide more accurate 10-year and 30-year risk estimates for adults aged 30 to 79 years. Pharmacists will note that low-density lipoprotein cholesterol (LDL-C) and nonhigh-density lipoprotein cholesterol (nonHDL-C) goals have returned as central pillars of therapy to guide clinical decision-making.^1,2

Specifically, to prevent a first event, LDL-C goals are set below 100 mg/dL for those at borderline or intermediate risk and below 70 mg/dL for high-risk patients, and secondary prevention for very high-risk individuals now targets an even more aggressive level of less than 55 mg/dL.

Although statin therapy remains the foundation of pharmacological lipid lowering, the 2026 update emphasizes the addition of nonstatin therapies when goals are not met or when statin-attributed muscle symptoms occur. Evidence-based options for treatment intensification now include ezetimibe, PCSK9 monoclonal antibodies such as alirocumab and evolocumab, and newer oral agents like bempedoic acid.

The guideline also highlights inclisiran as a second-line subcutaneous option for further LDL-C reduction, noting its unique dosing schedule of every 6 months after an initial titration. For specific conditions like familial chylomicronemia syndrome, the apoC3 inhibitor olezarsen is recommended as a novel adjunct to diet for reducing triglycerides and the risk of pancreatitis. Furthermore, for patients at high risk with persistently elevated triglycerides, icosapent ethyl may be considered based on the results of the REDUCE-IT (NCT01492361) trial.

“In general, lower LDL is better, especially for people at increased risk for a heart attack or stroke,” Pamela B. Morris, MD, FACC, FAHA, vice-chair of the guideline writing committee and the Paul V. Palmer chair of cardiovascular disease, said in a news release.² “Clinical trials have clearly demonstrated significant benefits for reduction in cardiovascular events when LDL-C levels are even lower than recommended in previous guidelines.”

Pharmacists play a critical role in managing medication safety and the complex landscape of drug-drug interactions, which the guideline details through specific risk mitigation strategies for statins. For instance, certain statins metabolized by cytochrome P450 3A4, such as simvastatin and lovastatin, require careful dose limitations or avoidance when combined with common cardiovascular medications like amiodarone, diltiazem, or amlodipine.^1,2

The guideline also advises against the routine measurement of creatine kinase or hepatic function for asymptomatic patients on statin therapy, recommending that these tests be reserved for those presenting with severe muscle symptoms or symptoms of hepatotoxicity. Managing statin-attributed muscle symptoms is another area of pharmacist focus, where the guidance suggests acknowledging patient concerns, excluding secondary causes, and exploring alternate statins or nondaily dosing of long-acting statins to maintain adherence.

Special considerations for patient management have been expanded, including a recommendation for statin therapy in patients living with HIV aged 40 to 75 years to reduce their unique cardiovascular risk, as demonstrated in the REPRIEVE (NCT02344290) trial. In pediatric care, universal cholesterol screening is now recommended for children between the ages of 9 and 11 years to identify familial hypercholesterolemia early.

Regarding reproductive health, the guideline suggests that persons of childbearing age who are not at high risk should generally stop statins 1 to 2 months before attempting to become pregnant, though an individualized benefit-risk discussion is advised for those with a history of clinical ASCVD or familial hypercholesterolemia.

READ MORE: Cardiology Resource Center

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REFERENCES

1. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. Published online March 13, 2026. doi:10.1016/j.jacc.2025.11.016

2. ACC/AHA issue updated guideline for managing lipid, cholesterol. News release. ACC. March 13, 2026. Accessed March 24, 2026. https://www.acc.org/About-ACC/Press-Releases/2026/03/13/18/01/ACCAHA-Issue-Updated-Guideline-for-Managing-Lipids-Cholesterol