Prognosis and Risk Factors in Patients With Asymptomatic Aortic Stenosis and Their Modulation by Atorvastatin (20 mg)

Wolfgang Dichtl, MD, PhDa, Hannes Franz Alber, MDa, Gudrun Maria Feuchtner, MDb, Florian Hintringer, MDa, Markus Reinthaler, MDa, Thomas Bartel, MDa, Alois Süssenbacher, MDa, Wilhelm Grander, MDa, Hanno Ulmer, PhDc, Otmar Pachinger, MDa, Silvana Müller, MDa

Received 2 March 2008; received in revised form 26 April 2008; accepted 26 April 2008. published online 07 July 2008.
Corrected Proof

The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 ± 1.2 years. Patients’ prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal–pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

a Clinical Department of Cardiology, Medical University Innsbruck, Innsbruck, Austria

b Clinical Department of Radiology, Medical University Innsbruck, Innsbruck, Austria

c Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria

Corresponding author: Tel: 43-512-504-81307; fax: 43-512-504-22767

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I don’t know if this study is relevant, but I’m posting it in case anyone is interested.

Marilyn

You sound like you know as much as I do. AS and CAD share some of the same risk factors, and are both progressive diseases characterized by inflammation and lipid deposition.There is some evidence that statins slow progression of AS. As you suggest, this could be partly due to their antiinflammatory effects. That kind of thing is hard to quantify, though.

As I recall, Mayo views A sclerosis in people under 65 as red flag and independent risk factor.

“It was comments like those that led to the anti-Merck and Schering ‘hysteria’ on Wall Street, according to Bernstein Research analyst Tim Anderson. ‘In isolation,’ Anderson says, ‘the results probably would have led to a share price rise for SGP and MRK, but largely due to negative comments from prominent cardiologist Steve Nissen, share prices declined.”

So Tim Anderson thought that the ENHANCE Trial was good news for Merck and Schering Plough . . . Either he has no clue, or he’s trying to curry favor with the companies.

I don’t see how the comments of this analyst are worth a hill of beans, anyway.

You read my mind.