The correct answer is: D. Add evolocumab 140 mg subcutaneously every two weeks

Answer D is the best choice for this patient. Per the 2018 ACC/AHA multisociety cholesterol guideline, this patient has residual cardiovascular risk based on her LDL-C remaining above 100 mg/dL despite maximally tolerated statin and ezetimibe therapy. The patient's Dutch Lipid Score is 6 or "probable" that she has Heterozygous Familial Hypercholesterolemia (HeFH) especially since secondary causes have been ruled out.¹ Patients with familial hypercholesterolemia (FH) are at significant risk of having an early ASCVD event and the use of 10-year risk estimators, such as the Pooled Cohort Equation, is not applicable to these patients. In this case, a PCSK9 inhibitor (evolocumab) should be used as add-on therapy in this patient with probable HeFH.¹

Answer A is not the best choice. Icosapent ethyl reduced cardiovascular disease in patients with triglycerides 150-499 mg/dL in addition to established cardiovascular disease or type 2 diabetes mellitus plus two cardiovascular risk factors.² This option is not appropriate as her triglyceride level is only 85 mg/dL.

Answer B is not the best option for this patient. Per 2018 AHA/ACC multisociety cholesterol guideline, fenofibrate is reserved for patients with severe hypertriglyceridemia (fasting triglycerides ≥500 mg/dL and especially when greater than 1000 mg/dL) in combination with a low-fat diet, avoidance of refined carbohydrates and alcohol consumption to prevent acute pancreatitis.¹ In addition, fenofibrate is not FDA approved to lower LDL-C in addition to statin therapy. This patient does not meet these criteria because her triglyceride level is 85 mg/dL.

Answer C is not best option. According to the 2018 ACC/AHA multisociety cholesterol guideline, this patient is in the severe hypercholesterolemia statin benefit group given her baseline LDL-C was greater than 190 mg/dL. She was appropriately treated with high intensity statin as well as ezetimibe, but per the ACC/AHA guideline, she still needs additional LDL-C lowering therapy as her LDL-C remains above the threshold of 100 mg/dL.¹ Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor recently approved by the United States Food and Drug Administration (FDA).³ In addition, the bempedoic acid and ezetimibe combination was also recently approved by the FDA.⁴ However, their use was not addressed in the 2018 ACC/AHA guideline as they were not commercially available yet. Both are an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C.^5,6 While this patient's LDL-C is still above 100 mg/dL, bempedoic acid may reduce LDL-C below this threshold. Bempedoic acid reduces LDL-C by approximately 15%, but only a small subset of patients used the combination ezetimibe, bempedoic acid statin in clinical studies. Therefore, data are still limited on the LDL-C lowering effects from using all three agents together.^5,6 Because cardiovascular events outcome data with bempedoic acid are lacking, an alternative agent with proven cardiovascular event reduction would be preferred.

References

1. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:3168-3209.
2. Bhatt D, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.
3. Center for Drug Evaluation and Research. Drug Trials Snapshots: NEXLETOL (U.S. Food and Drug Administration website). 2020. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-nexletol . Accessed 03/30/2020.
4. Important Safety Information (nexletolhcp.com website). 2020. Available at: https://www.nexletolhcp.com/dosing/. Accessed 03/30/2020.
5. Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of bempedoic acid vs. placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease: the CLEAR Wisdom randomized clinical trial. JAMA 2019;322:1780-8.
6. Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study. Atherosclerosis 2018;277:195–203.