Scottish Aortic Stenosis and Lipid Lowering Trial - SALTIRE
The goal of the SALTIRE trial was to evaluate the effect of lipid-lowering with atorvastatin compared with placebo with on progression/regression on calcific aortic stenosis.
Lipid-lowering with atorvastatin compared with placebo will halt progression and/or induce regression on calcific aortic stenosis.
Patients Enrolled: 155
Mean Follow Up: Median 25 months
Mean Patient Age: Mean age 68 years
Age ≥18 years, calcific aortic stenosis, an aortic-jet velocity of ≥2.5 m/second, and aortic-valve calcification on echocardiography.
Active or chronic liver disease, history of alcohol or drug abuse, severe mitral-valve stenosis, severe mitral or aortic regurgitation, left ventricular dysfunction, planned aortic-valve replacement, intolerance of statins, statin therapy or a potential benefit from statin therapy per the treating physician, baseline total cholesterol <150 mg per deciliter, presence of a permanent pacemaker or cardiodefibrillator, women of child-bearing potential without contraception.
Change in aortic-jet velocity and aortic-valve calcium score.
Composite clinical endpoint, including death from cardiovascular causes, aortic-valve replacement, or hospitalization attributable to severe aortic stenosis, and each component of the composite
Patients with calcified aortic stenosis were randomized in a double-blind manner to atorvastatin (80 mg/day, n=77) or placebo (n=78). At baseline and annually thereafter, patients underwent Doppler echocardiography to assess progression or regression of aortic jet velocity and underwent computed tomography to assess aortic-valve calcium score. Patients started on open-label statin therapy underwent scanning and were withdrawn from the study.
Median follow-up was 25 months. At baseline, the median aortic valve calcium score was 5920 AU, and mean aortic jet velocity was 3.43 m/sec. LDL cholesterol was reduced 53% to 63 mg/dL in the atorvastatin group, but did not change in the placebo group from 130 mg/dl (p<0.001). Total cholesterol was also reduced in the atorvastatin group (132 mg/dl) but not in the placebo group (209 mg/dl; p<0.001).
Change in aortic-jet velocity did not differ at follow-up between the atorvastatin and placebo groups (0.2 m/sec/yr in each group, p=0.95), nor did change in aortic-valve calcium score (1564 AU in atorvastatin group vs 1648 AU in placebo group, p=0.80). The clinical composite endpoint occurred in 13% of the atorvastatin group and 21% of the placebo group (p=0.19). Among the components of the composite, aortic valve replacement occurred in 11% and 19% (p=0.17), death from CV causes in 3% each, and hospitalization for severe aortic stenosis in 3% and 5% (p=0.73), respectively.
Among patients with calcific aortic stenosis, lipid-lowering therapy with atorvastatin was not associated with progression or regression of calcified aortic stenosis compared with placebo.
Previous large-scale randomized trials have established the role of statin therapy in reducing clinical events among patients at risk for coronary heart disease or following acute coronary syndromes. Given these findings and the association of calcified aortic stenosis with both hypercholesterolemia and coronary heart disease, the study sought to address whether lipid lowering with statins would also halt progression or induce regression of calcified aortic stenosis. Despite reductions in LDL and total cholesterol, there was no impact on calcified aortic stenosis with atorvastatin. There was also no correlation between LDL level and progression of aortic stenosis.
Cowell SJ, et al. A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis. N Engl J Med 2005;352:2389-97.
Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Noninvasive Imaging, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound
Keywords: Acute Coronary Syndrome, Follow-Up Studies, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Calcinosis, Coronary Disease, Heptanoic Acids, Hypercholesterolemia, Calcium, Pyrroles, Echocardiography, Doppler, Tomography
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