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Management of drug-resistant hypercholesterolemia

Hypercholesterolemia is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Statins are used as first-line therapy in most clinical settings (eg, primary and secondary prevention of ASCVD, treatment of familial hypercholesterolemia [FH]). Patients whose low-density lipoprotein cholesterol (LDL-C) remains elevated despite a statin and other therapies that are commonly started (ie, ezetimibe and/or proprotein convertase subtilisin kexin 9 [PCSK9] inhibitors) are said to be drug-resistant. This topic will discuss the evaluation and management of these patients.

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Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease

Lowering low-density lipoprotein cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease (CVD) in people without established CVD. This approach to CVD prevention is called primary prevention. The rationale for LDL-C reduction is based upon clinical trial evidence that lowering of LDL-C in patients across a broad range of LDL-C levels reduces a patient's risk of CVD [1].

CVD in this context refers to fatal or nonfatal myocardial infarction, acute coronary syndrome, sudden cardiac death, coronary artery revascularization, stroke, and peripheral arterial disease.

The decision about whether to lower LDL-C with pharmacotherapy incorporates both LDL-C level and a patient's estimated 10-year CVD risk. These factors help guide shared decision-making (ie, risk and benefit) discussions between patients and their providers.

This topic reviews the management and evidence for LDL-C lowering in patients for the purpose of primary CVD prevention. Such management and evidence in patients with established disease is discussed separately. (See "Management of low-density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

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