ACC Recommendations on the Role of Nonstatin Therapies for Lowering LDL-C

An expert consensus statement from the American College of Cardiology (ACC) on the role of nonstatin therapies for maintaining low-density lipoprotein cholesterol (LDL-C) levels to manage atherosclerotic cardiovascular disease (ASCVD) risk was published in the Journal of the American College of Cardiology.

Newer nonstatin therapy options include ezetimibe, alirocumab or evolocumab, bempedoic acid or bile acid sequestrant, and inclisiran. These medications reduce intestinal cholesterol absorption, increase the number of LDL receptors to clear the amount of circulating LDL-C, and inhibit hepatic cholesterol synthesis, respectively

This expert panel convened in 2021 in order to address current gaps in care. The statement addresses questions regarding in which patients and situations are newer nonstatin therapies appropriate.

The authors recommended for all patients to be evaluated for adherence to lifestyle modification and current therapy, for side effects, and cost of therapy. Some patients may benefit from referral to a lipid specialist, especially in the setting of intolerance, or to a dietitian or nutritionist.

For patients with clinical ASCVD, high-intensity statin therapy should be initiated among those aged 75 years or younger. During clinical trials, these patients were found to have additional cardiovascular outcome benefits from adding ezetimibe, alirocumab, or evolocumab to their therapeutic regimen.

The expert panel recommended that patients who do not achieve at least a 50% reduction in LDL-C concentration and who have an LDL-C concentration below 55 mg/dL should be evaluated for adherence to lifestyle modifications and statin therapies. For patients who are still not reaching treatment goals with maximum guideline-recommended statin therapies, these patients may be considered candidates for the addition of nonstatin therapies.

For patients without clinical ASCVD or those who have genetic causes of elevated LDL-C, such as familial hypercholesterolemia, the expert panel recommended similar treatment protocols of statin therapy, evaluation for lifestyle factors, and the addition of nonstatin therapies for patients who are still not meeting treatment goals.

For the subset of patients who are intolerant to at least 2 statin therapies, ezetimibe and/or alirocumab or evolocumab may be considered as an alternative first-line therapy for patient groups after risk stratification. Recommended second-line options included bempedoic acid, inclisiran, or bile acid sequestrant, depending on patient characteristics.

Certain patient groups, such as those with heart failure, end-stage renal disease, and pregnant women, require individualized care. Clinicians should keep in mind that ezetimibe is not recommended for patients with hepatic impairment.

“Since the publication of the 2018 America Heart Association/ACC/multisociety cholesterol guidelines, several newer nonstatin agents have demonstrated LDL-C–lowering efficacy, have received Food and Drug Administration approval, and are commercially available for management of at-risk patients,” the panel wrote. “Recommendations attempt to provide practical guidance for clinicians and patients regarding the use of nonstatin therapies to further reduce ASCVD risk in situations not covered by the guideline until such time as the scientific evidence base expands and cardiovascular outcomes trials are completed with newer agents for ASCVD risk reduction.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. Published online August 25, 2022. doi:10.1016/j.jacc.2022.07.006