Higher Lp(a) drives earlier onset and faster pressure-gradient progression in calcific aortic stenosis, review finds, with RNA-based agents the emerging therapeutic hope (Am J Med 2025)

Calcific aortic stenosis is a complex process that involves several factors, including genetics, lipid infiltration, inflammation, and hemodynamic stress. This process begins at an early age and progresses throughout one's lifetime. Lipoprotein (a), or Lp(a), has been shown to drive progression of aortic stenosis in several studies. Additionally, analyses have demonstrated that a higher serum level of Lp(a) is associated with earlier onset of aortic stenosis and faster progression of mean pressure across the aortic valve. The current cornerstone medications to lower low-density lipoprotein do not have a meaningful impact on Lp(a) levels. In this article, we will review current therapeutics that are in development to lower serum Lp(a), including several that involve ribonucleic acid modification. Although these novel therapeutics are promising, it is to be determined whether lowering serum Lp(a) correlates to reduced calcific aortic stenosis and improved cardiovascular outcomes.