Prevention of calcific aortic valve stenosis-fact or fiction?
Valve replacement is the only long-term effective treatment for calcific aortic valve stenosis. However, this treatment is aimed only at patients with advanced leaflet disease and symptoms of left ventricular obstruction. Over the past 15 years, our understanding of the pathogenesis of calcific aortic stenosis has changed significantly: away from a passive degenerative disease to an active process involving endothelial dysfunction, lipid accumulation, an inflammatory infiltrate, and a regulated process of calcification. Since many of the same processes are characteristic of atherosclerosis, trials have been undertaken to test whether medical therapy (statins, renin-angiotensin inhibition) can prevent or alter the disease course. Although retrospective and non-randomized studies suggested a positive effect with statins, benefit has not been seen in perspective randomized controlled trials, although two major studies are still in progress. 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 that might target different pathways in this disease process. In addition, we need to define the optimal timing and duration of therapy for this chronic slowly progressive disease; treatments aimed at the early disease process may be ineffective with end-stage tissue changes.
Cawley
Peter J
PJ
Department of Medicine, University of Washington, Seattle, USA.
Otto
Catherine M
CM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D050197:Atherosclerosis / Q000188:drug therapy / Q000517:prevention & control; D000069059:Atorvastatin; D002114:Calcinosis / Q000188:drug therapy / Q000517:prevention & control; D009202:Cardiomyopathies / Q000517:prevention & control; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin