What’s Next for Lipoprotein(a)?: Key Points

Koschinsky ML, Soffer DE, Boffa MB.
What’s Next for Lipoprotein(a)? A National Lipid Association Report From an Expert Panel Discussion. J Clin Lipidol 2024;Jul 1:[Epub ahead of print].

The following are key points to remember from an expert panel discussion convened by the National Lipid Association (NLA) in November 2023 to address unmet needs regarding lipoprotein(a) [Lp(a)]:

  1. The panel of 12 members included fundamental researchers and clinicians in cardiology, endocrinology, lipidology, and primary care.
  2. The panel acknowledged a need for the development of educational materials in a variety of formats to raise awareness of Lp(a) among clinicians, patients, and other stakeholders.
  3. The NLA endorses measurement of Lp(a) at least once in all adults as part of routine clinical practice. The recommendation was published in a focused update to the 2019 NLA scientific statement on use of Lp(a) in clinical practice in April 2024. The panel acknowledges this is currently an aspirational recommendation. Canadian and European professional societies have published similar recommendations.
  4. Until Lp(a) testing becomes widespread, it is reasonable to incorporate Lp(a) testing into order sets for specific conditions (e.g., aortic valve replacement for calcific aortic stenosis).
  5. Well-defined recommendations for managing Lp(a) are needed. These are anticipated to develop as results from clinical trials of targeted Lp(a) therapy become available.
  6. Fundamental research is needed to elucidate the metabolism of Lp(a)—hepatic production, clearance, renal involvement, pathogenic mechanism, and additional unknown aspects.
  7. The most pressing clinical question is whether targeted lowering of Lp(a) reduces atherosclerotic cardiovascular disease (ASCVD) risk in a secondary prevention population. Several international phase 3 randomized controlled trials are ongoing, which should provide an answer to that question.
  8. If benefit in secondary prevention is established, then the role of targeted Lp(a) lowering in patients with subclinical ASCVD should be investigated.
  9. Other clinical questions relate to Lp(a) targets, potential adverse effects of therapeutic Lp(a) lowering, Lp(a) modifiers, interindividual variation, whether and when repeat Lp(a) measurement might be warranted, and the relative contributions to disease of Lp(a) and low-density lipoprotein cholesterol in patients with extreme Lp(a) elevations.
  10. In primary care, current barriers to Lp(a) testing include noncoverage by insurance companies, a lack of robust clinical decision support tools, insufficient clinician education, and a need for clearer therapeutic management guidelines. The latter have been clarified in the focused update to the 2019 NLA scientific statement, and will be further clarified when results of ongoing clinical trials on targeted Lp(a) reduction become available.
  11. More registries and studies are needed in the pediatric population, particularly regarding Lp(a) and pediatric stroke. Lp(a) can be measured as early as age 5 or along with a lipid profile (at age 9-11 years), as recommended by the American Association of Pediatrics and the American Heart Association.
  12. The Lp(a)HORIZON trial, using pelacarsen, is scheduled for completion in 2025. The panel anticipates the trial will, for the first time, demonstrate whether specifically lowering Lp(a) (with medication) reduces cardiovascular endpoints in the context of secondary prevention.

Clinical Topics: Dyslipidemia, Prevention, Advanced Lipid Testing, Lipid Metabolism

Keywords: Atherosclerosis, Lipoprotein(a), Secondary Prevention

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