AHA Scientific Statement Promotes Expanded Use of Lipoprotein Apheresis

Laurence S. Sperling, MD

Credit: USNews

A new scientific statement from the American Heart Association (AHA) has shed light on the underutilized implementation of lipoprotein apheresis as a therapeutic intervention for children and adults with familial hypercholesterolemia (FH) and elevated levels of lipoprotein(a) [Lp(a)] and low-density lipoprotein cholesterol (LDL-C).¹

This procedure, which effectively reduces levels of LDL-C and Lp(a) by 65% to 85% in a single session, is an emerging critical option for patients with FH who do not respond adequately to conventional therapies, particularly those at high risk for atherosclerotic cardiovascular disease (ASCVD).

“In this scientific statement on lipoprotein apheresis, we review the historical development, available devices, indications, efficacy, vascular effects, outcomes data, use in special populations, availability, access, cost, and patient perspectives,” wrote writing committee chair Laurence S. Sperling, MD, the Katz Professor in Preventive Cardiology at Emory University School of Medicine.

FH ranks within the most common genetic disorders of lipid metabolism but remains notably underdiagnosed and undertreated worldwide.² The US Food and Drug Administration (FDA) has approved lipoprotein apheresis for FH after lifestyle intervention and maximal tolerated LDL-C–lowering medications at various thresholds.³ It is the only FDA-approved treatment for Lp(a) lowering, but only in patients with FH and LDL-C >100 mg/dL, but remains underused for high-risk patients with suboptimal lipoprotein control.

The LIPOSORBER LA-15 system has been approved for these patient patients in whom dietary intervention and maximum drug therapy have been either ineffective or not tolerated: homozygous FH (HoFH) with LDL-C level >500 mg/dL; heterozygous FH (HeFH) withLDL-C level ≥300 mg/dL; or HeFH with LDL-C level≥100 mg/dL, Lp(a) level ≥60 mg/dL, and documented coronary artery disease (CAD) or peripheral artery disease (PAD).⁴

A single lipid apheresis session has been shown to reduce LDL-C levels by up to 85%, with the extent of reduction depending on the volume of plasma or blood treated, but frequent sessions are required to maintain lower time-averaged LDL-C levels due to rapid rebound.¹ Lipid apheresis devices target apoB-containing lipoproteins and improve various vascular and inflammatory biomarkers.

However, although lipid apheresis has been shown to enhance endothelial function, reduce coagulation factors, and lower inflammatory markers, it remains unclear whether these effects improve outcomes independent of lipoprotein reduction. Additionally, the reduction in triglycerides and HDL-bound proteins is temporary, with most levels rebounding within 24 hours.

Most findings on the cardiovascular benefits of lipid apheresis are reported from observational studies, as randomized controlled trials are limited given ethical concerns about withholding an evidence-based therapy in a high-risk population. These studies have shown that lipid apheresis can reduce major adverse cardiovascular events (MACE) by approximately 50% to 85%, with the greatest benefit in patients with elevated Lp(a) and LDL-C levels.

Although mainly observational, the writing committee indicated the strength of this evidence is derived from multiple factors, including the use of individuals as their own controls, the consistency of ASCVD benefits across multiple populations, and multiple years of follow-up.

Lipid apheresis has also been explored as a treatment for focal segmental glomerulosclerosis (FSGS), with mixed outcomes, ranging from full remission to no benefit, with children experiencing some promising results. The treatment is widely available in European countries like Germany, but access remains limited in the United States, with some patients living hundreds of miles from the nearest center.

The writing committee indicated nearly 11,000 to 15,000 Americans with FH could qualify for lipid apheresis, yet fewer than 400 are currently receiving the treatment, reflecting significant barriers in access and awareness. They called for more referrals to existing centers and the creation of additional centers—only 33 U.S. states have lipid apheresis facilities—along with better patient education about the benefits of the procedure, to address this gap.

Although more costly than the most expensive LDL-lowering therapies, lipid apheresis is notably less expensive than the other available treatments for patients who fail these therapies. The annual cost of lipid apheresis in the US ranges from $50,000 to $150,000, depending on the setting and payer, compared with lomitapide or evinacumab, which can cost up to $450,000 annually.

Overall, the committee noted these barriers to care, such as treatment frequency, travel distance, cost, and concerns about insurability complicate access to lipid apheresis and underscore the need for comprehensive research on the impact of social determinants of health and long-term adherence to lipid apheresis.

“Although cost-effectiveness and quality of life effects are important factors to consider in shared decision-making regarding treatment, lipid apheresis may provide substantial clinical benefit for many high-risk patients, in whom it is frequently underused,” the committee wrote.

References

1. _{Gianos E, Duell PB, Toth PP, et al. Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. Published online October 7, 2024. doi:10.1161/ATV.0000000000000177}
2. _{Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. J Am Coll Cardiol. 2020;75(20):2553-2566. doi:10.1016/j.jacc.2020.03.057}
3. _{Feingold KR. Lipoprotein Apheresis. [Updated 2023 Feb 19]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425700/}
4. _{Kaneka Medical America. Liposorber LA-15 System: Instructions for Use:Special HDE Supplement for H120005 and H170002. Kaneka Corpora-tion; 2022.}