Do Statins Improve Outcomes and Delay the Progression of Non-Rheumatic Calcific Aortic Stenosis?

Study Questions:

Does therapy with a statin slow the progression of nonrheumatic aortic stenosis (AS)?

Methods:

A meta-analysis of studies was performed comparing statin therapy with placebo or no treatment on outcomes and on echocardiographic parameters of AS progression, using a search of Medline and PubMed through January 2010. Two reviewers independently abstracted information on study design (prospective vs. retrospective, randomized vs. nonrandomized), and study and participant characteristics. Fixed- and random-effects models were used. A priori subanalyses separately assessed the effect of statins in low-quality (retrospective or nonrandomized) and in high-quality (prospective or randomized) studies.

Results:

Meta-analysis identified 10 studies with a total of 3,822 participants (2,214 nonstatin-treated and 1,608 statin-treated); five studies were classified as prospective and five as retrospective; three trials were randomized, whereas seven studies were nonrandomized. No significant differences were found in all-cause mortality, cardiovascular mortality, or in the need for aortic valve surgery. Lower-quality (retrospective or nonrandomized) studies showed that, in statin-treated patients, the annual increase in peak aortic jet velocity and the annual decrease in aortic valve area were lower, but this was not confirmed by the analysis in high-quality (prospective or randomized) studies. Statins did not significantly affect the progression over time of peak and mean aortic gradient.

Conclusions:

The authors concluded that currently available data do not support the use of statins to improve outcomes and to reduce disease progression in nonrheumatic calcific AS.

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 Vmax 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.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Valvular Heart Disease, Congenital Heart Disease, CHD and Pediatrics and Quality Improvement, Nonstatins, Statins

Keywords: Follow-Up Studies, Heart Defects, Congenital, Sclerosis, Azetidines, Heart Valve Diseases, Disease Progression


< Back to Listings