Download PDF
Semin Thromb Hemost
DOI: 10.1055/a-2768-2477
Review Article

Clinical Response to Elevated Lipoprotein(a): Practical Approach for Risk Management in the Absence of Targeted Therapies

Authors

  • Fabian Sanchis-Gomar

    1   Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California
    2   Department of Health Sciences, University of Burgos, Burgos, Spain

  • Giuseppe Lippi 

    3   Section of Clinical Biochemistry, School of Medicine, University of Verona, Verona, Italy
Further Information
   Permissions and Reprints

Abstract

Lipoprotein(a) (Lp(a)) is a genetically determined, lifelong cardiovascular risk factor strongly associated with atherosclerotic cardiovascular disease (ASCVD) despite optimal low-density lipoprotein cholesterol (LDL-C) lowering. The current management is challenged by the absence of outcome-proven Lp(a)-specific therapies. Statins, ezetimibe, bempedoic acid, and lifestyle interventions have little or no effect on Lp(a). Statins may modestly raise levels; niacin is now contraindicated as it has not been shown to reduce cardiovascular or all-cause mortality, while PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors and inclisiran reduce Lp(a) concentrations by approximately 20 to 30%, though this effect remains secondary to their LDL-C-lowering effect. The only U.S. Food and Drug Administration (FDA)-approved therapy specifically addressing Lp(a) is lipoprotein apheresis, which reduces Lp(a) levels by 60 to 75%, but is restricted to specific patient populations due to invasiveness, high cost, and limited availability. Future promise lies in RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small-interfering RNAs (olpasiran, lepodisiran, SLN360), which achieve 80 to 95% sustained Lp(a) reductions. Large outcome trials will determine whether this biochemical efficacy translates into tangible clinical benefits. Current guidelines now recommend one-time lifetime Lp(a) measurement, treating ≥125 nmol/L (≥50 mg/dL) as a risk-enhancing factor. High or extreme elevations, especially with ASCVD, mandate aggressive LDL-C lowering, optimization of modifiable risk factors, family cascade screening, and apheresis or referral to RNA-therapy trials in select cases. Thus, while therapeutic options remain limited, systematic measurement and risk stratification are ethically justified to prepare for the imminent arrival of Lp(a)-targeted therapies.

Keywords

lipoprotein(a) - Lp(a) - cardiovascular risk - therapy


Publication History

Received: 20 September 2025

Accepted: 08 December 2025

Accepted Manuscript online:
11 December 2025

Article published online:
22 December 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA