Lp(a) - Little "a" with a Big Impact 

Written by Chad Travers, MD, FACC

We have all known individuals that appear to be perfectly healthy and then suffer a heart attack or stroke.  Research is showing that Liproprotein(a) – Lp(a) or LP little A – is emerging as a pertinent risk factor for cardiovascular disease (CVD).  Determining a patient’s Lp(a) value may influence discussions that focus on your patient’s ability to reduce personal risk factors for a heart attack or stroke.

What to Know about Lp(a):

• This particular type of lipoprotein is comprised of an extra protein, apolipoprotein(a) or apo(a), that is stickier than other types of LDL; making it more likely to cause blockages and blood clots
• Research suggests that Lp(a) is an independent risk factor linked to heart disease, even in younger adults and otherwise healthy people with no known cardiovascular risks
• Elevated Lp(a) level is largely genetically influenced but may be influenced by diet as well
• Despite having lower LDL-C, patients could still have high Lp(a) – testing for Lp(a) is important
• Testing for Lp(a) can be done by a simple blood draw in a doctor’s office

Who Should be Tested for Lp(a):

• Patients who are at high risk for CVD include:
  • Premature heart disease or family history of premature heart disease
  • Family history of high Lp(a)
  • Familial hypercholesterolemia (FH)
  • Recurrent cardiovascular events in spite of LDL lowering

Treatment Options for Lp(a)

Lp(a) is a presumed cardiac risk factor, however there are currently no approved therapies to lower it.  Common lipid lowering therapies have largely proven ineffective when treating Lp(a).  Statins do not reduce Lp(a) and may even cause a slight increase.  Niacin has shown modest reductions in Lp(a) but is not currently approved for treatment of Lp(a) and has not been shown to reduce cardiovascular risk.

For years, Bryan Heart has had a strong clinical research presence and dedication to bringing state-of-the-art treatments to our patients.  With this in mind, I am currently serving as a Principal Investigator for a Phase 3 trial evaluating the efficacy and safety of olpasiran, an investigational therapy that lowers Lp(a) through RNA interference.

Research Study Overview

Eligible participants will be randomized to olpasiran or matching placebo administered once every 12 weeks by subcutaneous injection. Average follow-up duration will be around four years. The study drug will not replace any existing treatments that the patient may be receiving, and will be given in addition to standard of care treatment. Patients should be on optimal lipid-lowering therapy prior to entering the study.  Following the initial screening visit, patients and providers will be blinded to their Lp(a) value and lipid panel.  In order to maintain integrity of the study, patients will be instructed to avoid having these labs checked during their participation in the study.  Statin-intolerant patients are eligible for participation, with proper documentation of previous tired therapies.

Study Inclusion Criteria Include:

• Age 18 to ≤ 85 years
• Lp(a) ≥ 200 nmol/L (~90 mg/dl) during screening
• History of ASCVD as evidenced by history of either:
  • Myocardial infarction (MI) (presumed type 1 event due to plaque rupture and/or
  • Coronary revascularization by percutaneous coronary intervention (PCI) with stenting AND any of the following:
    • Age ≥ 65 years
    • Diabetes mellitus (type 1 or type 2)
    • Ischemic stroke
    • Symptomatic peripheral arterial disease with either
      • (a) intermittent claudication with ankle-brachial index (ABI) < 0.85, or
      • (b) peripheral arterial revascularization or amputation due to atherosclerotic disease
    •  Residual stenosis > 50% in any major vessels
    • Multivessel PCI (ie, ≥ 2 vessels, including branch arteries)

Study Exclusion Criteria Include:

• Severe renal dysfunction
• Active liver disease, known hepatitis, or hepatic dysfunction
• History of hemorrhagic stroke or major bleeding disorder
• Planned cardiac surgery or arterial revascularization
• Severe heart failure
• Current, recent, or planned lipoprotein apheresis
• Previously received ribonucleic acid therapy specifically targeting Lp(a) (use of inclisiran is allowed)

Patients that are enrolled into the study will not be charged for their medication, nor have expenses related to study required testing (i.e. labs or ECGs).  Patients will also be reimbursed for reasonable travel expenses. 

For more information about this clinical trial, you are welcome to visit www.ClinicalTrials.gov (identifier: NCT05581303).  Phase 2 trial results have been published and can be found by referencing O’Donoghue et al., NEJM 2022.  For regular medical treatment outside of this study, your patients will be directed back to you.

If you would like to learn more about Lp(a) and its role in CVD, please call our office at 402-483-3333.  If you’d like additional information about this study or to refer a patient, please contact the study coordinators for Bryan Heart Research Services at 402-483-3291 (Andrew) or 402-483-3290 (Nicci).