Perspective:

Substantial evidence suggests that degenerative AS is an atherosclerotic lesion. In theory, lipid-lowering therapy would retard the progression of this atherosclerotic lesion, as it does coronary and cerebrovascular ones. Despite this, no large prospective study has been able to convincingly demonstrate this. This meta-analysis of previously performed studies appropriately concludes that persuasive data do not now exist to support the concept that a statin might slow the progression of AS. Unfortunately, demonstration of a beneficial effect (if it exists) might be impossible to prove––if therapy needs to be initiated before AS is far advanced. To explore this, examine some of the data that went into the meta-analysis. The SEAS trial was the largest trial to investigate this, with 1,873 patients randomly assigned to placebo or to simvastatin 40 mg plus ezetimibe 10 mg, with a mean follow-up of 52 months. The inclusion criterion was ‘mild-to-moderate’ AS, defined simply by V_max 2.5-4.0 m/s. That 30% of patients in this trial underwent aortic valve replacement within a little more than 4 years of an echocardiogram demonstrating only mild-to-moderate AS might be surprising, but for the vagaries of AS quantification. Rather, if many patients actually had more significant AS, pharmacotherapy might have been too little too late. Meanwhile, it seems unlikely that enough patients with truly mild AS––or even just aortic sclerosis––could be randomized and followed for a sufficient interval to test whether earlier pharmacotherapy is efficacious. Without conclusive positive studies, practitioners are left to weigh with their patients whether absence of proof should or should not be taken as proof of absence.