Title:Lipoprotein(a) Management: Pharmacological and Apheretic Treatment
VOLUME: 24 ISSUE: 10
Author(s):Ruth Hanssen and Ioanna Gouni-Berthold*
Affiliation:Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Kerpener Str. 62, 50937 Cologne, Polyclinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University of Cologne, Kerpener Str. 62, 50937 Cologne
Keywords:Antisense oligonucleotide, apolipoprotein (a), cardiovascular disease, lipoprotein (a), lipoprotein
apheresis.
Abstract:Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle with an
additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent
epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is
causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The
risk association between Lp(a) concentrations and CVD is still controversial but seems to be
continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a)
are genetically determined; desirable levels are < 50 mg/dl. A plasma concentration of 60
mg/dl is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment
for other cardiovascular risk factors. Extended-release niacin is an option for decreasing elevated
Lp(a) levels (by ~20-30%) but it is often poorly tolerated. Dietary measures, exercise
and lipid-lowering drugs such as statins and ezetimibe are without significant effect. In patients
with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis can decrease
Lp(a) concentrations. The method is expensive and impractical for most patients and
its feasibility depends mainly on the healthcare reimbursement system. Since no established
treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial that
evaluated whether decreasing Lp(a) concentrations translates to clinical benefits. Recently, an
antisense oligonucleotide against apo(a), IONIS-APO(a)Rx, has been shown to selectively
decrease Lp(a) by almost 80%. A phase 2 study with this drug has been completed in late
2015 and results are expected to be published soon.
