Real-World Decision-Making in LDL-C Lowering Therapy

Jun 25, 2025   |  Semenawit Burka, MD; Erin D. Michos, MD, FACC
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A 44-year-old Caucasian woman with a history of hypertension and prediabetes is referred to the cardiology clinic for evaluation and management of severe hypercholesterolemia. She reports a strong family history of hypercholesterolemia and premature coronary artery disease (CAD) on both her maternal and paternal sides. Notably, her father had early-onset CAD and another family member on her mother's side was similarly affected.

She recalls being diagnosed with significantly elevated cholesterol levels during childhood, with a maximum total cholesterol (TC) level of approximately 280 mg/dL at 11 years of age. Although she was briefly treated with statin therapy during adolescence, she discontinued it shortly thereafter and remained off lipid-lowering therapy until 2019, when her primary care provider identified TC level 458 mg/dL and initiated high-intensity statin therapy. She had no history of formal atherosclerotic disease testing prior to cardiology referral. Over the last 2 years, she has developed intermittent nonexertional and exertional chest pain. Her cardiac medications include rosuvastatin 20 mg daily and telmisartan 40 mg daily.

On examination, her body mass index (BMI) is 31.0 and blood pressure is 121/84 mm Hg. Physical examination findings are otherwise unremarkable.

A fasting lipid panel while receiving high-intensity statin therapy reveals TC level 251 mg/dL, triglyceride (TG) level 175 mg/dL, high-density lipoprotein cholesterol (HDL-C) level 35 mg/dL, and low-density lipoprotein cholesterol (LDL-C) level 181 mg/dL. Additional laboratory studies, including kidney function values, liver enzyme levels, thyroid-stimulating hormone level, and vitamin D level, are within the reference ranges except for hemoglobin A1c concentration 6%. Genetic testing for familial hypercholesterolemia has not yet been performed.

Her lifestyle history reveals poor dietary habits, with a preference for prepackaged foods, limited fruit and vegetable intake, and occasional fast food consumption. She reports riding horses for activity but does not engage in structured exercise.

Ezetimibe 10 mg daily is added, and further workup includes a coronary computed tomography angiogram (CTA) and advanced lipid testing. Her CTA has findings of multivessel nonobstructive CAD. Follow-up lipid panel results show improved values on dual therapy: TC level 193 mg/dL, TG level 131 mg/dL, HDL-C level 35 mg/dL, and LDL-C level 134 mg/dL. Her lipoprotein(a) (Lp[a]) level is markedly elevated at 237.5 nmol/L. Genetic testing confirms a single pathogenic variant in the low-density lipoprotein receptor (LDLR) gene.

Given suboptimal LDL-C level control and evidence of early CAD, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab is initiated. Two months later, her lipid panel reveals further improvement: TC level 167 mg/dL, TG level 131 mg/dL, HDL-C level 39 mg/dL, LDL-C level 106 mg/dL, and Lp(a) level 190 nmol/L. She remains asymptomatic at follow-up but continues to express challenges with dietary adherence and sustained lifestyle changes.

Which of the following are the next steps in optimizing her management of atherosclerotic cardiovascular disease (ASCVD) risk?

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