Universität zu Köln

Schreml, Julia and Gouni-Berthold, Ioanna (2017). Apolipoprotein(a) Antisense Oligonucleotides: A New Treatment Option for Lowering Elevated Lipoprotein(a)? Curr. Pharm. Design, 23 (10). S. 1562 - 1571. SHARJAH: BENTHAM SCIENCE PUBL LTD. ISSN 1873-4286

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Abstract

Background: Lipoprotein(a) [Lp(a)] is a particle similar to LDL that contains an additional protein called apolipoprotein(a) [apo(a)]. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) may be causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). While the risk association between Lp(a) concentrations and CVD is weak it seems to be continuous in shape and without an obvious threshold for Lp(a) levels. Methods: Circulating concentrations of Lp(a) are genetically determined and 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. Results: Extended-release niacin is the pharmacologic means of choice for decreasing elevated Lp(a) levels by similar to 20-30% but it is often poorly tolerated due to adverse reactions. Diet, exercise and lipid-lowering drugs such as statins, fibrates and ezetimibe are without effect. In patients with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis may be used to decrease Lp(a) concentrations. However, it is an expensive and impractical treatment for most patients and its feasibility depends on the healthcare reimbursement system of the respective country. Since no established treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial examining whether decreasing Lp(a) concentrations translates to clinical benefits. Conclusion: Recently, an antisense oligonucleotide against apo(a), IONIS-APO(a)Rx, has been shown to selectively decrease Lp(a) by similar to 80%. A phase 2 study with this drug has been completed in late 2015 and results are expected to be published soon.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schreml, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-246335
DOI:	10.2174/1381612823666170125160108
Journal or Publication Title:	Curr. Pharm. Design
Volume:	23
Number:	10
Page Range:	S. 1562 - 1571
Date:	2017
Publisher:	BENTHAM SCIENCE PUBL LTD
Place of Publication:	SHARJAH
ISSN:	1873-4286
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CORONARY-HEART-DISEASE; EXTENDED-RELEASE NIACIN; CARDIOVASCULAR-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; RISK-FACTOR; OXIDIZED PHOSPHOLIPIDS; NICOTINIC-ACID; APO-B-100-CONTAINING LIPOPROTEINS; REDUCES LIPOPROTEIN(A); PLASMA LIPOPROTEIN(A) Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24633