Is it acceptable to initiate a patient with hypercholesterolemia, whose parents have a history of hypercholesterolemia, on atorvastatin (HMG-CoA reductase inhibitor) 10 mg and ezetimibe (cholesterol absorption inhibitor) 10 mg?

From the Guidelines

Starting a patient on both atorvastatin 10 mg and ezetimibe 10 mg solely based on parental history of high cholesterol is not typically recommended as first-line therapy. The standard approach would be to begin with lifestyle modifications and a single agent, usually a statin like atorvastatin 10 mg alone, as recommended by the 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. Combination therapy with ezetimibe is generally reserved for patients who have not achieved target LDL levels with statin monotherapy, have documented atherosclerotic cardiovascular disease, or have very high baseline cholesterol levels. Before initiating any medication, the patient should undergo their own lipid panel testing to determine their actual cholesterol levels, and their overall cardiovascular risk should be assessed using established risk calculators, such as those discussed in the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. This approach allows for personalized treatment based on the patient's specific risk factors rather than family history alone. Some key points to consider include:

• The patient's own lipid profile and cardiovascular risk factors should guide treatment decisions
• Lifestyle modifications should be the foundation of treatment
• Statin therapy, such as atorvastatin 10 mg, is typically the first-line pharmacological treatment
• Ezetimibe may be added to statin therapy if the patient has not achieved target LDL levels or has very high baseline cholesterol levels
• The 2022 ACC expert consensus decision pathway provides guidance on the use of nonstatin therapies, including ezetimibe, in the management of atherosclerotic cardiovascular disease risk 1. If treatment is warranted, starting with a moderate-intensity statin like atorvastatin 10 mg and evaluating the response after 4-12 weeks would be more appropriate, adding ezetimibe later if needed to reach target LDL levels, as supported by the 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline 1.

From the FDA Drug Label

TABLE 8: Response to Ezetimibe Tablet and Atorvastatin Initiated Concurrently in Patients with Primary Hyperlipidemia (Mean % Change from Untreated Baseline*) Treatment (Daily Dose) N Total-C LDL-C Apo B Non-HDL-C Placebo 60 +4 +4 +3 +4 Ezetimibe Tablet 65 -14 -20 -15 -18 Atorvastatin 10 mg 60 -26 -37 -28 -34 Ezetimibe Tablet + Atorvastatin 10 mg 65 -38 -53 -43 -49

The combination of ezetimibe 10 mg and atorvastatin 10 mg can be used to treat patients with primary hyperlipidemia.

• The LDL-C reduction achieved with this combination is -53%, which is greater than that achieved with atorvastatin 10 mg alone (-37%).
• This combination is a viable treatment option for patients with high cholesterol, including those with a family history of high cholesterol. 2

From the Research

Treatment of High Cholesterol with Atorvastatin and Ezetimibe

• The combination of atorvastatin and ezetimibe is a common treatment for high cholesterol, as it has been shown to be effective in lowering low-density lipoprotein cholesterol (LDL-C) levels 3, 4, 5.
• Studies have demonstrated that the addition of ezetimibe to atorvastatin therapy can provide significant incremental reductions in LDL-C levels, allowing more patients to reach their lipid goals 6, 4, 5.
• The efficacy and safety of atorvastatin and ezetimibe combination therapy have been compared to double-dose statin monotherapy, with results showing that the combination therapy can significantly decrease LDL-C, non-high-density lipoprotein cholesterol, and total cholesterol levels 4.
• A study published in 2004 found that the addition of ezetimibe to atorvastatin therapy resulted in a significantly higher proportion of patients achieving their target LDL-C level goal of ≤100 mg/dL compared to atorvastatin monotherapy 5.
• Another study published in 2021 found that the combination of bempedoic acid, ezetimibe, and atorvastatin resulted in significant reductions in LDL-C, non-high-density lipoprotein cholesterol, and total cholesterol levels, with 90% of patients achieving LDL-C <70 mg/dL 6.

Dosage and Safety

• The dosage of atorvastatin and ezetimibe can vary depending on the patient's response to treatment and their individual risk factors 4, 5.
• Studies have shown that the combination of atorvastatin and ezetimibe is generally well-tolerated, with a safety profile similar to that of atorvastatin alone 4, 5.
• However, it is essential to monitor patients for potential adverse effects, such as laboratory-related adverse events, and to adjust the dosage accordingly 4.

Familial Hypercholesterolemia

• Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C and an increased risk of cardiovascular disease 7.
• Current guidelines recommend LDL-C targets for FH patients, including <100 mg/dL for adults or <70 mg/dL for adults with coronary heart disease or diabetes 7.
• The combination of atorvastatin and ezetimibe may be an effective treatment option for patients with FH, as it can help to achieve these recommended LDL-C targets 7, 3, 6.