Lipid-Lowering Therapy in Calcific Aortic Stenosis
Authors: Kwan L Chan, Koon Teo
Journal: New England Journal of Medicine (2005)

Background Calcific aortic stenosis is the commonest valvular heart condition seen in the western world and appears to be the result of an active inflammatory process closely resembling atherosclerosis. 1 hypothesised that (a) risk factors for atherosclerosis would predict, and (b) lipid-lowering therapy would retard, disease progression and clinical outcome in patients with calcific aortic stenosis.Objectives (i) To compare the magnitude and reproducibility of measures of valvular stenosis and calcification, (ii) to determine the effect of intensive lipidlowering therapy on disease progression and clinical outcome, and (iii) to describe predictors of disease progression and clinical outcome in patients with aortic stenosis.Methods These issues were addressed in the context of a randomised controlled trial of which I was study co-ordinator.In the Scottish Aortic stenosis and Lipid-lowering Therapy, Impact on REgression (SALTIRE) trial, 155 patients aged 68 ± 11 years (range 34-85) with aortic valve stenosis were randomised, and underwent helical computed tomography (CT) and Doppler echocardiography.Seventy-seven patients were assigned to atorvastatin 80 mg daily and 78 to matched placebo over a median period of 25 months.Of the 155 patients, 102 had detectable coronary artery calcification on CT with 48 of these patients being randomised to atorvastatin and 54 to placebo.Results (i) Stenosis severity: Doppler echocardiography demonstrated a mean aortic jet velocity of 3.45 ± 0.66 metres per second (m/s) and a peak gradient of 49 ± 11 millimetres of mercury (mmHg).Computed tomography and Doppler echocardiography showed good reproducibility.The median aortic valve calcium (AVC) score was 5858 Hounsfield units (HU) (interquartile range, 1555-14596) and this positively correlated with aortic jet velocity and peak gradient (r=0.54,p<0.0001 for both), (ii) Disease progression: Aortic jet velocity increased by 0.199 ± 0.210 m/s per year in the atorvastatin group and 0.203 ± 0.208 m/s per year in the placebo group (p=0.95;adjusted mean difference, 0.002; 95% confidence interval (CI)), (-0.066 to +0.070 m/s/yr).Progression in valvular calcification was 22 ± 21% per year in the atorvastatin group, and 22 ± 20% per year in the placebo group (p=0.93;ratio of post-treatment AVC score, 0.998; 95% CI, 0.947 to 1.050).The rate of change in coronary artery calcification was 26% per year (0.234 ± 0.037 log arbitrary units/yr (LogAU/yr); n=39) in the atorvastatin group and 18% per year (0.167 ± 0.034 LogAU/yr; n=49) in the placebo group: geometric mean difference of +7% per year (95% CI, -3% to +18%; p=0.18).(iii) Lipid-lowering'.Atorvastatin reduced serum low-density lipoprotein (LDL) cholesterol (-53%; p<0.001) and C-reactive protein (CRP) (-49%; p<0.001) concentrations whilst there was no change with placebo (-7% and +17%; p>0.95 for both).There was no correlation between serum LDL concentrations and the progression of aortic stenosis or coronary calcification, (vi) Predictors of disease progression and outcome'.Aortic valve disease progression was predicted by age, sex, height, hypertension, serum brain natriuretic peptide (BNP) concentration, and baseline valve disease severity.Clinical outcome was predicted by baseline and rate of progression of aortic stenosis severity and serum ACE Angiotensin-converting enzyme ANOVA Analysis of variance AS Aortic stenosis AU Arbitrary units AVA Aortic valve area AVC Aortic valve calcium AVR Aortic valve replacement BNP Brain natriuretic peptide CI Confidence interval CRP C-reactive protein CT Computed tomography CVA Cerebrovascular accident research supervisors; Dr Nicholas Boon, for agreeing to appoint me as research fellow to co-ordinate the SALTIRE trial, and guide