Quest for pharmacotherapy in aortic valve stenosis: the lipid hypothesis

Aortic stenosis was first described by the French surgeon and anatomist Lazare Riviere in 1663. While the last decade has seen impressive advances in our ability to treat aortic valve stenosis invasively and percutaneously, significant issues remain with regards to the optimal timing of valve replacement, periprocedural risks and long-term durability. There therefore remains major interest in developing medical treatments to halt or slow progression of aortic stenosis, which could obviate the need for surgical intervention altogether. A stitch in time saves nine; however, no pharmacotherapies are currently proven to be effective for the treatment of calcific aortic valve stenosis (CAVS). Atherogenic apolipoprotein B-containing lipoproteins, such as low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)), have clearly been implicated in the pathogenesis of aortic stenosis, particularly in the early initiation phase. However, LDL cholesterol lowering with statins or ezetimibe failed to modify progression of aortic valve stenosis in multiple randomised clinical trials (SEAS, SALTIRE and ASTRONOMER). Attention has instead switched to Lp(a), with a growing body of epidemiology, genetics and prospective imaging studies having built a convincing case for elevated Lp(a) levels being associated with an increased incidence of aortic stenosis, …