Cholesterol Management in Difficult-to-Treat Patients

There are several patient populations that are difficult to manage, including those with familial hypercholesterolemia, statin intolerance, or an inadequate response to statin therapy.

In recent years, significant advancements have been made in treatment aimed at lowering low-density lipoprotein cholesterol (LDL-C) levels to improve cardiovascular disease (CVD) outcomes.1 Unfortunately, there are still several patient populations that are difficult to manage, including those with familial hypercholesterolemia (FH), statin intolerance, or an inadequate response to statin therapy. Each of these patient populations, as well as potential treatment options for each group, will be reviewed in this article.

FH is characterized by elevated LDL-C levels and is often associated with early-onset coronary heart disease (CHD).1 Although homozygous FH is very rare, heterozygous FH has been found to affect 1 in 300 to 500 adults. Diagnosis of FH is based on the results of a patient’s physical examination, LDL-C levels, and their personal as well as family history of CHD. Currently, it is recommended to include lipid screening for FH in all patients in late childhood to early adulthood.

A suggested algorithm for the treatment of FH is summarized in Figure 1. According to the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, initiation of a high-intensity statin is recommended in all patients with FH due to their elevated LDL-C levels and increased risk for CHD events.1 In patients who do not tolerate statin therapy or continue to have elevated LDL-C levels despite statin therapy, addition of a nonstatin medication should be considered. This is especially true in patients with known CVD, diabetes mellitus, or other CVD risk factors. 

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In FH patients who are not well controlled on statin therapy, various medication options are available.1 Although not studied in FH patients, ezetimibe was found to reduce LDL-C levels and CVD events when added to statin therapy in a recent review. Because of this, ezetimibe should be considered a second-line agent. In addition, consideration should be given to the recently approved pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which have demonstrated to be very effective in reducing LDL-C levels. Although lacking studies, bile-acid resins and niacin may also be options to further reduce LDL-C levels in FH patients. Lastly, apheresis of LDL-C can be considered in FH patients as a last-line therapy.

Patients that do not tolerate statin medications are another population that can be challenging for providers to manage.1 Unfortunately, statin intolerance is a relatively common problem. Statin-associated muscle symptoms (SAMS) are the most common adverse events associated with statin therapy, although change in cognitive function and development of diabetes mellitus have also been reported. Various studies have found mixed results regarding the rate of SAMS in patients on statin therapy.