Lipoprotein apheresis to address residual risk in recurrent atherosclerotic events

Abstract

Background/Synopsis

Optimal medical therapy may be insufficient in attenuating cardiovascular risk in individuals with elevated Lipoprotein(a) (Lp(a)). Lipoprotein apheresis can play a role in such cases.

Objective/Purpose

To describe a unique case of accelerated atherosclerosis refractory to aggressive LDL-C lowering.

Methods

Medical record review.

Results

A 66-year-old male, non-smoker, with controlled type 2 diabetes mellitus, familial hypercholesterolemia (FH), peripheral vascular disease, and recurrent acute coronary syndrome (ACS) presented to our lipid clinic. His mother had severe hyperlipidemia. Baseline lipid panel from 40 years prior showed a total cholesterol of 330 mg/dL and LDL-C of 220 mg/dL. He took rosuvastatin and ezetimibe for over 20 years. His first ACS event five years prior required a left anterior descending artery (LAD) stent. At this time, icosapent ethyl was added and his lipid profile was controlled with apolipoprotein B of 60 mg/dL. However, months later, he required carotid endarterectomy for severe carotid stenosis. Two years later, another LAD stent was placed for new disease in the setting of an LDL-C of 54 mg/dL. After this event, PCSK9 inhibitor was prescribed but denied by insurance. One year later, repeat lipid panel showed: LDL-C 37 mg/dL, apolipoprotein B 66 mg/dL, Lp(a) 297 nmol/L, and hs-CRP 2.6mg/L. PCSK9 inhibitor was denied again so bempedoic acid was added. Lipid apheresis was recommended but denied by insurance. The following year, he had severe two-vessel coronary disease including in-stent restenosis of a prior LAD stent, necessitating coronary artery bypass graft. Two days after surgery, evolocumab was approved and initiated. However, one month later, he required a stent to his bypass graft. Eventually he received insurance approval for lipoprotein apheresis and had significant LDL-C and Lp(a) reduction.

This case demonstrates that despite optimal lipid and anti-platelet therapy, risk factor control, and invasive treatment, recurrent ACS and plaque progression ensued. This was likely mediated by high Lp(a). Lipoprotein apheresis is the only FDA approved treatment for elevated Lp(a), now with an approved FDA indication for Lp(a) ≥ 60 mg/dL or ≥ 130 nmol/L with coronary or peripheral artery disease, noting a cardiovascular event reduction greater than 75% in such patients. Phase 3 trials are ongoing for Lp(a) lowering agents which will inform future treatment.

Conclusions

Patients with FH, elevated Lp(a) and hs-CRP represent an ultra high-risk profile for aggressive atherosclerosis. For our patient, delays in PCSK9 inhibitor and apheresis initiation likely influenced disease progression. Lipoprotein apheresis has demonstrated a reduction in cardiovascular events.