1Department of Microbiology, Meenakshi Ammal Dental College and Hospital, Meenakshi Academy of Higher Education and Research
2Department of General Medicine, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research
3Meenakshi College of Arts and Science, Meenakshi Academy of Higher Education and Research
4Arulmigu Meenakshi College of Nursing, Meenakshi Academy of Higher Education and Research
5Meenakshi College of Pharmacy, Meenakshi Academy of Higher Education and Research
6Meenakshi College of Physiotherapy, Meenakshi Academy of Higher Education and Research
Aim: To assess the effects of antisense oligonucleotide as lipoprotein(a) [Lp(a)] decrease on the disease process of calcific aortic valve stenosis (CAVS).
Background: High Lp(a) is a known, genetically determined risk factor of CAVS and it leads to the calcification of the leaflet, inflammation, and expedited hemodynamic degradation. Up to now, any medical treatment has not proved itself able to delay the CAVS. Antisense oligonucleotides against apolipoprotein(a) hold some promise as they have powerful Lp(a) reducing effects, but their role in the progression of valvular disease has been uncertain.
Methods: This observational, multicentric study involved 420 adults who had mild- to moderate- CAVS and high Lp(a) (>60mg/dl). The patients were given 18 months of antisense oligonucleotide treatment. Baseline, 9 months and 18 months Aortic valve area (AVA), peak velocity, and mean transvalvular gradient were measured using serial echocardiography. They were compared with a historical matching control cohort of untreated patients with similar levels of Lp(a). The main measure of change was annualization of the AVA; secondary measures were changes in the hemodynamic gradients and calcium biomarkers.
Results: The level of Lp(a) decreased by an average of 78%. AVA deterioration was much lower in the antisense group than in the controls (Annualized 0.06 vs. 0.12 cm²/year; p < 0.001). The progression of mean gradient and inhibited the calcium deposition biomarkers was also reduced in treated patients.
Conclusion: There is a significant reduction in the Lp(a) by the use of antisense oligonucleotide therapy and a reduced progression rate of CAVS indicates the disease-modifying potential of that therapy to be evaluated in randomized trials.
Keywords: Antisense Oligonucleotides, Lipoprotein(a), Calcific Aortic Valve Stenosis, CAVS, Lp(a), Aortic Valve Area
How to cite this article: Amritkumar P, Jayannan, Devi PN, Vasanthapriya J, Pugazhendhi S, Divya S. Antisense Oligonucleotides Lowering Lipoprotein(a): Effects on Calcific Aortic Valve Stenosis Progression. Int J Drug Deliv Technol. 2026;16(10s): 90-95; DOI: 10.25258/ijddt.16.10s.12
Source of support: Nil.
Conflict of interest: None