When do you refer a patient for hypercholesterolemia (high cholesterol)?

From the Guidelines

Referral for hypercholesterolemia is recommended when patients have severely elevated lipid levels, such as LDL cholesterol exceeding 190 mg/dL, despite maximum statin therapy, or when they have complex presentations that require specialized care. Consider referral to a lipid specialist when patients have familial hypercholesterolemia (especially with LDL >190 mg/dL), or when they experience intolerable side effects to multiple statins even at lower doses or with alternative dosing regimens 1. Patients with triglycerides >500 mg/dL despite treatment, those with complex dyslipidemias, or individuals with premature cardiovascular disease (men <55, women <65) should also be referred. Additionally, consider referral for patients with significant comorbidities like chronic kidney disease or HIV that complicate lipid management. Early specialist involvement is important because specialized treatments like PCSK9 inhibitors, ezetimibe combinations, or clinical trial options may be necessary to achieve target lipid levels and reduce cardiovascular risk in these challenging cases.

Some key considerations for referral include:

• LDL cholesterol levels exceeding 190 mg/dL despite maximum statin therapy
• Familial hypercholesterolemia, especially with LDL >190 mg/dL
• Intolerable side effects to multiple statins
• Triglycerides >500 mg/dL despite treatment
• Complex dyslipidemias
• Premature cardiovascular disease (men <55, women <65)
• Significant comorbidities like chronic kidney disease or HIV

According to the 2022 ACC expert consensus decision pathway, referral to a lipid specialist is recommended for patients with ASCVD and baseline LDL-C ≥190 mg/dL who did not achieve ≥50% reduction in LDL-C and LDL-C <70 mg/dL (or non–HDL-C <100 mg/dL) on maximally tolerated statin therapy in combination with nonstatin therapy 1. The 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol also supports referral for patients with severe hypercholesterolemia (LDL-C ≥190 mg/dL) who do not respond adequately to first-line treatments 1.

In terms of treatment options, PCSK9 inhibitors, such as alirocumab and evolocumab, may be considered for patients with heterozygous familial hypercholesterolemia (HeFH) and LDL-C ≥100 mg/dL despite maximally tolerated statin and ezetimibe therapy 1. Ezetimibe may also be used as an adjunct to diet to reduce LDL-C, non-HDL-C, ApoB, and TC in patients with primary hyperlipidemia, either alone or in combination with statin therapy 1.

Overall, referral for hypercholesterolemia is an important consideration for patients with severely elevated lipid levels or complex presentations, and early specialist involvement can help reduce cardiovascular risk and improve patient outcomes.

From the Research

Referral for Hypercholesterolemia

Referral for hypercholesterolemia is considered in the following cases:

• Patients with phenotypic severe hypercholesterolemia (SH), low-density lipoprotein-cholesterol (LDL-c) ≥ 190 mg/dl, atherosclerotic cardiovascular disease (ASCVD) or adults 40-75 years with diabetes with risk factors or 10-year ASCVD risk ≥ 20% 2
• Patients who have not achieved the LDL-C targets recommended by guidelines despite being on statin therapy 3
• Patients with very high cardiovascular risk, such as those with diabetes or peripheral artery disease, who may benefit from an aggressive LDL-C-lowering approach 3
• Patients who are intolerant to statin therapy or have contraindications to statin use 4

Indications for Specialty Care Referral

Specialty care referral is indicated for:

• Patients with severe hypercholesterolemia who require maximally tolerated statin therapy and/or other lipid-lowering therapies 2
• Patients with high or very high cardiovascular risk who require aggressive LDL-C-lowering therapy 3, 4
• Patients who have not achieved lipid goals despite being on statin therapy and require additional therapeutic approaches 4

Benefits of Specialty Care Referral

Benefits of specialty care referral include:

• Improved likelihood of being prescribed evidence-based cholesterol-lowering therapy, such as statins or PCSK9 inhibitors 2
• Increased likelihood of achieving lipid goals and reducing cardiovascular risk 2, 3
• Access to newer lipid-lowering therapies, such as ezetimibe and PCSK9 inhibitors, which may be beneficial for patients with high or very high cardiovascular risk 5, 6, 4