Should a patient with a history of myocardial infarction (MI) on Aspirin (ASA) 81mg and Crestor (Rosuvastatin) 20mg with an elevated Low-Density Lipoprotein (LDL) level of Hyperlipidemia be treated to further lower their LDL?

From the Guidelines

You should consider further lowering the LDL level in your patient who experienced a myocardial infarction despite being on aspirin 81mg and atorvastatin 20mg with an LDL of 1.16 mmol/L (approximately 45 mg/dL). For patients with established atherosclerotic cardiovascular disease, especially those who have had a recent event, more aggressive lipid lowering is often beneficial, as supported by the 2024 recommendations on the optimal use of lipid-lowering therapy in established atherosclerotic cardiovascular disease and following acute coronary syndromes: a position paper of the international lipid expert panel (ILEP) 1. Consider increasing the atorvastatin dose to 40-80mg daily or adding ezetimibe 10mg daily as a second agent. If these measures don't achieve sufficient reduction or are not tolerated, a PCSK9 inhibitor like evolocumab or alirocumab could be considered, as suggested by the 2024 recommendations 1. The rationale for more aggressive lipid lowering is that patients with established coronary disease remain at high risk for recurrent events, and clinical trials have demonstrated that "lower is better" for LDL levels in secondary prevention, with no clear lower threshold where benefit diminishes, as noted 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. Additionally, the recurrent event despite seemingly adequate LDL levels suggests that your patient may have residual risk factors requiring more intensive management of all cardiovascular risk factors, including optimizing blood pressure control, diabetes management if applicable, and lifestyle modifications. Some key points to consider include:

• The importance of early access to statin therapy and lipid-lowering combination therapy with non-statin drugs, as highlighted in the 2024 recommendations 1
• The potential benefits of upfront lipid-lowering combination therapy in patients with established pre-event atherosclerotic CVD, as suggested by the 2024 position paper 1
• The need to individualize therapy and consider the addition of nonstatin agents, such as ezetimibe or PCSK9 inhibitors, in patients who do not achieve sufficient reduction in LDL-C with statin therapy alone, as noted in the 2022 ACC expert consensus decision pathway 1.

From the FDA Drug Label

INDICATIONS AND USAGE EZETIMIBE Tablets is indicated (1): • In combination with a statin, or alone when additional low density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)

The patient is already on a statin (atorvastatin 20mg, also known as crestor) and has an LDL level of 1.16. The FDA drug label does not provide a specific LDL target level. However, considering the patient had a myocardial infarction, it may be beneficial to further reduce LDL levels.

• The use of ezetimibe in combination with a statin is indicated to reduce elevated LDL-C levels.
• The decision to push the LDL level further down should be based on individual patient assessment and clinical judgment, considering the benefits and risks of further LDL reduction. 2

From the Research

Patient's Current Condition

• The patient is currently on ASA 81 and Crestor 20mg with an LDL level of 1.16 mmol/L.
• The patient has experienced a myocardial infarction despite being on statin therapy.

LDL Level Reduction

• According to 3, the physiologically normal levels of LDL-C are in the 30- to 70-mg/dl range, and atherosclerosis progression is halted and coronary heart disease events are minimized when statin therapy is used to drive down the LDL-C to a range of about 30 to 50 mg/dl.
• 4 suggests that ezetimibe, a cholesterol absorption inhibitor, can lead to additional LDL cholesterol reduction and decreased ASCVD risk when added to statin therapy.
• 5 and 6 also support the use of ezetimibe and PCSK9 inhibitors to further reduce LDL-C levels and regress atherosclerosis.

Treatment Considerations

• The patient's current LDL level is 1.16 mmol/L, which is approximately 44.7 mg/dl, already within the target range suggested by 3.
• However, considering the patient's history of myocardial infarction, further reduction of LDL-C levels may be beneficial to minimize the risk of future adverse cardiovascular events, as suggested by 4, 5, and 6.
• The use of ezetimibe or PCSK9 inhibitors in addition to statin therapy may be considered to achieve further LDL-C reduction, as recommended by 4, 5, and 6.

Safety Considerations

• 3 notes that statins appear to be safe even when LDL-C is lowered to about 50 mg/dl, although more robust outcome and safety data are required, particularly for PCSK9 inhibitors and very low LDL-C levels.
• 5 and 7 suggest that ezetimibe, PCSK9 inhibitors, and other non-statin therapies have benign side-effect profiles and are generally well tolerated.