Correspondence

Lipid-Lowering Therapy in Calcific Aortic Stenosis

N Engl J Med 2005; 353:1066-1067September 8, 2005

Article

To the Editor:

The Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE), reported by Cowell et al. (June 9 issue),1 is a prospective study of the effect of lipid-lowering therapy in aortic stenosis. The result is important but does not convincingly refute the importance of lipids in the development of aortic stenosis because the study is susceptible to type II errors, owing to the small sample size and relatively short follow-up. In addition, it is surprising that only 5 of 155 patients in SALTIRE had a bicuspid aortic valve, which is the most common predisposing condition for aortic stenosis.2,3 Even among patients in the seventh decade of life, bicuspid aortic valves account for about half the cases of severe aortic stenosis requiring aortic-valve replacement.2 It is inexplicable that patients with a bicuspid valve were so underrepresented in the study. We agree with the authors that there continues to be a “need for a long-term, large-scale, randomized, controlled trial of intensive lipid-lowering therapy in patients with calcific aortic stenosis, particularly in those with early, mild disease” and in those with a bicuspid aortic valve.

Kwan L. Chan, M.D.
University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada
kchan@ottawaheart.ca

Koon Teo, M.D.
McMaster University, Hamilton, ON L8N 3Z6, Canada

3 References

1. 1

   Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005;352:2389-2397
   Full Text | Web of Science | Medline

2. 2

   Davies MJ, Treasure T, Parker DJ. Demographic characteristics of patients undergoing aortic valve replacement for stenosis: relation to valve morphology. Heart 1996;75:174-178
   CrossRef | Web of Science | Medline

3. 3

   Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005;111:920-925
   CrossRef | Web of Science | Medline

Author/Editor Response

We thank Drs. Chan and Teo for their comments. The narrow 95 percent confidence intervals accompanying the estimates of the treatment difference, together with concordant computed tomographic and echocardiographic data, make a type II error unlikely. We have certainly ruled out a treatment benefit of the magnitude reported in previous observational studies.1 There is evidence of publication bias, with negative findings underrepresented in the literature.2 A large observational study3 (involving 242 subjects) with a long follow-up (4.5 years) also demonstrated no effect of statin therapy.

The prevalence of bicuspid aortic stenosis varies widely: rates as low as 5 percent have been reported.4 The reports cited by Drs. Chan and Teo are selective surgical case series. It is notoriously difficult to diagnose bicuspid aortic valves by echocardiography once they are calcified. In our trial, a bicuspid aortic valve was not an exclusion criterion and was diagnosed only when the appearance was unequivocal. When there was uncertainty, the valve was classified as tricuspid. We concede that many patients in our trial had an unrecognized bicuspid aortic valve, especially given the 42 percent prevalence in our previous surgical series.5

David E. Newby, M.D.
David B. Northridge, M.D.
Nicholas A. Boon, M.D.
University of Edinburgh, Edinburgh EH16 4SB, United Kingdom
d.e.newby@ed.ac.uk

5 References

1. 1

   Rosenhek R. Statins for aortic stenosis. N Engl J Med 2005;352:2441-2443
   Full Text | Web of Science | Medline

2. 2

   Samal AK, Berman AE, Kuruvanka TS, Nasca PF, Ventura HO, Gilliand YE. Effect of statin therapy in the progression of moderate to severe calcific aortic stenosis. Circulation 2002;106:Suppl II:II-640 abstract.
   

3. 3

   Antonini-Canterin F, Popescu BA, Huang G, et al. Progression of aortic valve sclerosis and aortic valve stenosis: what is the role of statin treatment? Ital Heart J 2005;6:119-124
   Medline

4. 4

   Turri M, Thiene G, Bortolotti U, Milano A, Mazzucco A, Gallucci V. Surgical pathology of aortic valve disease: a study based on 602 specimens. Eur J Cardiothorac Surg 1990;4:556-560
   CrossRef | Web of Science | Medline

5. 5

   Chui MC, Newby DE, Panarelli M, Bloomfield P, Boon NA. Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy? Clin Cardiol 2001;24:52-55
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Félix Gil-Dones, Verónica M. Darde, Sergio Alonso-Orgaz, Luis F. Lopez-Almodovar, Laura Mourino-Alvarez, Luis R. Padial, Fernando Vivanco, Maria G. Barderas. (2011) Inside human aortic stenosis: A proteomic analysis of plasma. Journal of Proteomics
   CrossRef