Pharmacotherapy of Aortic Stenosis-Success or Failure?

Abstract

Aortic stenosis (AS) is a degenerative valvular disease that has, until recently, been considered to be a progressive and the most importantly unmodifiable process. However, recent histopathologic studies have clearly reported that the both development and progression of AS is based on an biochemically active process which is mediated by a chronic inflammation (featured by many similarities with atherosclerosis) and includes inflammatory-cell infiltrates, lipoproteins, lipids and factors responsible for calcification (extracellular-bone-matrix proteins and bone mineral). Targeted drug therapy to prevent the progression of calcific AS disease should ideally be based on the knowledge of risk factors and the molecular pathogenesis of the disease. Treatment trials using various drugs have been undertaken to test whether medical therapy (statins, renin-angiotensin inhibition and anti-osteoporosis drugs) can prevent or beneficially modify the disease course. Although retrospective and non-randomized studies suggested a positive effect of statins, benefit has not been seen in perspective randomized controlled trials. Inhibition of renin-angiotensin has shown discordant results in retrospective studies with no randomized controlled data published. In the future, we need to consider other medical therapies (antiosteoporosis drugs are attractive candidates) that might target different pathways in this disease process. Additionally, we need to detect the optimal moment to start statin therapy for this chronic slowly progressive disease; treatments aimed at the early disease process (pre-obstructive form of aortic sclerosis) may be ineffective with end-stage tissue changes.