HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   HELP   |    More Options

Please sign in for full text and personal services

Previous Volume 352:2389-2397 June 9, 2005 Number 23 Next

Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Rosenhek, R. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Find Similar Articles PubMed Citation

ABSTRACT

Background Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression.

Methods In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score.

Results Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130±30 mg per deciliter in the placebo group and fell to 63±23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199±0.210 m per second per year in the atorvastatin group and 0.203±0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, –0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3±21.0 percent per year in the atorvastatin group, and 21.7±19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050).

Conclusions Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.

Source Information

From the Department of Cardiology, Royal Infirmary, Edinburgh (S.J.C., D.E.N., P.B., N.A.B.); Public Health Sciences, University of Edinburgh Medical School, Edinburgh (R.J.P.); the Department of Radiology, Borders General Hospital, Melrose, Roxburghshire, United Kingdom (J.R.); and the Department of Cardiology, Western General Hospital, Edinburgh (D.B.N.).

Address reprint requests to Dr. Newby at the Department of Cardiology, Royal Infirmary, Old Dalkeith Rd., Little France, Edinburgh EH16 4SU, United Kingdom, or at d.e.newby{at}ed.ac.uk.

Full Text of this Article

Related Letters:

Lipid-Lowering Therapy in Calcific Aortic Stenosis
Chan K. L., Teo K., Newby D. E., Northridge D. B., Boon N. A.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:1066-1067, Sep 8, 2005. Correspondence

This article has been cited by other articles:

• Chua, D., Kalb, K. (2006). Statins and Progression of Calcified Aortic Stenosis. The Annals of Pharmacotherapy 40: 2195-2199 [Abstract] [Full Text]  
• Aboulhosn, J., Child, J. S. (2006). Left Ventricular Outflow Obstruction: Subaortic Stenosis, Bicuspid Aortic Valve, Supravalvar Aortic Stenosis, and Coarctation of the Aorta. Circulation 114: 2412-2422 [Full Text]  
• Johnson, R. C., Leopold, J. A., Loscalzo, J. (2006). Vascular Calcification: Pathobiological Mechanisms and Clinical Implications.. Circ. Res. 99: 1044-1059 [Abstract] [Full Text]  
• Rajamannan, N. M. (2006). Calcific aortic stenosis: a disease ready for prime time.. Circulation 114: 2007-2009 [Full Text]  
• Weiss, R. M., Ohashi, M., Miller, J. D., Young, S. G., Heistad, D. D. (2006). Calcific Aortic Valve Stenosis in Old Hypercholesterolemic Mice. Circulation 114: 2065-2069 [Abstract] [Full Text]  
• Budoff, M. J., Achenbach, S., Blumenthal, R. S., Carr, J. J., Goldin, J. G., Greenland, P., Guerci, A. D., Lima, J. A.C., Rader, D. J., Rubin, G. D., Shaw, L. J., Wiegers, S. E. (2006). Assessment of Coronary Artery Disease by Cardiac Computed Tomography: A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114: 1761-1791 [Full Text]  
• Ortlepp, J R, Pillich, M, Mevissen, V, Krantz, C, Kimmel, M, Autschbach, R, Langebartels, G, Erdmann, J, Hoffmann, R, Zerres, K (2006). APOE alleles are not associated with calcific aortic stenosis. Heart 92: 1463-1466 [Abstract] [Full Text]  
• Houslay, E S, Cowell, S J, Prescott, R J, Reid, J, Burton, J, Northridge, D B, Boon, N A, Newby, D E, on behalf of the Scottish Aortic Stenosis and Lipi, (2006). Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial. Heart 92: 1207-1212 [Abstract] [Full Text]  
• Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Faxon, D. P., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B. (2006). ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Developed in Collaboration With the Society of Cardiovascular Anesthesiologists Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.. J Am Coll Cardiol 48: e1-e148 [Full Text]  
• Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Faxon, D. P., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B. (2006). ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Developed in Collaboration With the Society of Cardiovascular Anesthesiologists Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 48: 598-675 [Full Text]  
• O'Brien, K. D. (2006). Pathogenesis of Calcific Aortic Valve Disease: A Disease Process Comes of Age (and a Good Deal More). Arterioscler. Thromb. Vasc. Bio. 26: 1721-1728 [Abstract] [Full Text]  
• Helske, S., Syvaranta, S., Lindstedt, K. A., Lappalainen, J., Oorni, K., Mayranpaa, M. I., Lommi, J., Turto, H., Werkkala, K., Kupari, M., Kovanen, P. T. (2006). Increased Expression of Elastolytic Cathepsins S, K, and V and Their Inhibitor Cystatin C in Stenotic Aortic Valves. Arterioscler. Thromb. Vasc. Bio. 26: 1791-1798 [Abstract] [Full Text]  
• Osman, L., Yacoub, M. H., Latif, N., Amrani, M., Chester, A. H. (2006). Role of Human Valve Interstitial Cells in Valve Calcification and Their Response to Atorvastatin. Circulation 114: I-547-I-552 [Abstract] [Full Text]  
• Osman, L., Chester, A. H., Amrani, M., Yacoub FRS, M. H., Smolenski MD, R. T. (2006). A Novel Role of Extracellular Nucleotides in Valve Calcification: A Potential Target for Atorvastatin. Circulation 114: I-566-I-572 [Abstract] [Full Text]  
• Shao, J.-S., Cai, J., Towler, D. A. (2006). Molecular Mechanisms of Vascular Calcification: Lessons Learned From The Aorta. Arterioscler. Thromb. Vasc. Bio. 26: 1423-1430 [Abstract] [Full Text]  
• Briand, M., Lemieux, I., Dumesnil, J. G., Mathieu, P., Cartier, A., Despres, J.-P., Arsenault, M., Couet, J., Pibarot, P. (2006). Metabolic Syndrome Negatively Influences Disease Progression and Prognosis in Aortic Stenosis. J Am Coll Cardiol 47: 2229-2236 [Abstract] [Full Text]  
• Newby, D E, Cowell, S J, Boon, N A (2006). Emerging medical treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors, or both?. Heart 92: 729-734 [Abstract] [Full Text]  
• Katz, R., Wong, N. D., Kronmal, R., Takasu, J., Shavelle, D. M., Probstfield, J. L., Bertoni, A. G., Budoff, M. J., O'Brien, K. D. (2006). Features of the Metabolic Syndrome and Diabetes Mellitus as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation 113: 2113-2119 [Abstract] [Full Text]  
• Lichtenstein, S. V. (2006). Closed heart surgery: Back to the future. J. Thorac. Cardiovasc. Surg. 131: 941-943 [Full Text]  
• Son, B.-K., Kozaki, K., Iijima, K., Eto, M., Kojima, T., Ota, H., Senda, Y., Maemura, K., Nakano, T., Akishita, M., Ouchi, Y. (2006). Statins Protect Human Aortic Smooth Muscle Cells From Inorganic Phosphate-Induced Calcification by Restoring Gas6-Axl Survival Pathway. Circ. Res. 98: 1024-1031 [Abstract] [Full Text]  
• Liebe, V., Brueckmann, M., Borggrefe, M., Kaden, J. J. (2006). Statin therapy of calcific aortic stenosis: hype or hope?. Eur Heart J 27: 773-778 [Abstract] [Full Text]  
• Drolet, M.-C., Roussel, E., Deshaies, Y., Couet, J., Arsenault, M. (2006). A High Fat/High Carbohydrate Diet Induces Aortic Valve Disease in C57BL/6J Mice. J Am Coll Cardiol 47: 850-855 [Abstract] [Full Text]  
• Allison, M. A., Cheung, P., Criqui, M. H., Langer, R. D., Wright, C. M. (2006). Mitral and Aortic Annular Calcification Are Highly Associated With Systemic Calcified Atherosclerosis. Circulation 113: 861-866 [Abstract] [Full Text]  
• Takagi, H., Umemoto, T., Krasuski, R. A., Griffin, B. P., Afshinnia, F., Rahimtoola, S. H., Evangelista, A., Tornos, P., Permanyer-Miralda, G. (2006). Vasodilators in Aortic Regurgitation. NEJM 354: 300-303 [Full Text]  
• Rahimtoola, S. H. (2006). The Year in Valvular Heart Disease. J Am Coll Cardiol 47: 427-439 [Full Text]  
• Chan, K. L., Teo, K., Newby, D. E., Northridge, D. B., Boon, N. A. (2005). Lipid-Lowering Therapy in Calcific Aortic Stenosis. NEJM 353: 1066-1067 [Full Text]  
• Malik, I. (2005). JournalScan. Heart 91: 1118-1120 [Full Text]  
• (2005). Statins Do Not Slow Calcific Aortic Stenosis. Journal Watch Cardiology 2005: 2-2 [Full Text]  
• Rosenhek, R. (2005). Statins for Aortic Stenosis. NEJM 352: 2441-2443 [Full Text]