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Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease
- Source :
- Clinical Kidney Journal
- Publication Year :
- 2020
- Publisher :
- Oxford University Press, 2020.
-
Abstract
- Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate 100 mg/g were excluded from Phase 2 trials and those with ‘significant kidney disease’ will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.
- Subjects :
- cardiovascular risk
medicine.medical_specialty
dyslipidaemia
medicine.medical_treatment
030232 urology & nephrology
Renal function
030204 cardiovascular system & hematology
Gastroenterology
Peritoneal dialysis
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
cardiovascular disease
lipoprotein(a)
Internal medicine
Medicine
AcademicSubjects/MED00340
Editorial Comments
Transplantation
biology
business.industry
PCSK9
Lipoprotein(a)
medicine.disease
pelacarsen
Nephrology
biology.protein
business
Nephrotic syndrome
chronic kidney disease
Kidney disease
Lipoprotein
Subjects
Details
- Language :
- English
- ISSN :
- 20488513, 20488505, and 04023552
- Volume :
- 13
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Clinical Kidney Journal
- Accession number :
- edsair.doi.dedup.....5c79fe7fb72f62ed577703273ea0e71e