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Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.
- Source :
-
New England Journal of Medicine . 1/16/2020, Vol. 382 Issue 3, p244-255. 12p. - Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.<bold>Methods: </bold>We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).<bold>Results: </bold>The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.<bold>Conclusions: </bold>APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.). [ABSTRACT FROM AUTHOR]
- Subjects :
- *CARDIOVASCULAR diseases
*DISEASE risk factors
*AORTIC stenosis
*PLATELET count
*ANTILIPEMIC agents
*CHOLESTEROL
*COMPARATIVE studies
*DOSE-effect relationship in pharmacology
*LIPOPROTEINS
*RESEARCH methodology
*MEDICAL cooperation
*NUCLEOTIDES
*REGRESSION analysis
*RESEARCH
*EVALUATION research
*RANDOMIZED controlled trials
*BLIND experiment
Subjects
Details
- Language :
- English
- ISSN :
- 00284793
- Volume :
- 382
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- New England Journal of Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 141268719
- Full Text :
- https://doi.org/10.1056/NEJMoa1905239