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

https://doi.org/10.1016/j.amjcard.2008.04.060Get rights and content

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.

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Study population

Of 120 patients consecutively referred to our echocardiography laboratory for the evaluation of asymptomatic calcified aortic stenosis, 50 were enrolled from November 2003 to November 2005 and followed until February 2008. Baseline and follow-up assessments after every 12 months included clinical examination, transthoracic echocardiography, multidetector computed tomography, and the biochemical analysis of blood. Patients aged >18 years with calcific aortic stenosis, mean systolic gradients of

Patients

Of 120 patients screened, 50 were randomized, and 47 were ultimately enrolled in the study (Figure 1). Three patients were excluded from the study (1 patient in the placebo group was diagnosed with gastric cancer 3 months after randomization, 1 patient randomized to placebo was lost during follow-up, and 1 patient stopped medication with atorvastatin because of intolerance without any increase in creatinine kinase or hepatic enzyme levels). Baseline characteristics are listed in Table 1. No

Discussion

The main findings of TASS are as follows: (1) The natural histories of patients with asymptomatic aortic stenosis were poor. (2) In addition to established hemodynamic risk factors, the degree of AVC, systemic inflammation (mirrored by increased plasma CRP levels), and elevated NT-proBNP levels predicted MACEs (the latter only in univariate analysis). (3) Age or the presence of concomitant coronary artery calcium did not significantly influence prognosis. (4) Although limited by small sample

Acknowledgment

The help of Anna Muck throughout the study is greatly appreciated.

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