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Circulation. 2003;108:839-843
Published online before print July 28, 2003, doi: 10.1161/01.CIR.0000084539.58092.DE
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(Circulation. 2003;108:839.)
© 2003 American Heart Association, Inc.


Clinical Investigation and Reports

Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy

Koichi Node, MD, PhD; Masashi Fujita, MD; Masafumi Kitakaze, MD, PhD; Masatsugu Hori, MD; James K. Liao, MD

From the Cardiovascular Division (K.N.), Department of Medicine, Saga Medical School, Saga, Japan; Department of Internal Medicine and Therapeutics (M.F., M.H.), Osaka University Graduate School of Medicine, Osaka, Japan; Division of Cardiology (M.K.), National Cardiovascular Center, Osaka, Japan; and Cardiovascular Division (J.K.L.), Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence and reprint requests to James K. Liao, MD, Brigham & Women’s Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139 (e-mail jliao{at}rics.bwh.harvard.edu), or Koichi Node, MD, PhD, Cardiovascular Division, Department of Medicine, Saga University School of Medicine, 5-1-1 Nabeshima, Saga, 849-8501 Japan (e-mail nodekoi@post.saga-med.ac.jp).

Received November 12, 2001; de novo received April 24, 2003; accepted May 6, 2003.

Background— Chronic heart failure is associated with inflammation and neurohormonal imbalance. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, exert anti-inflammatory and vascular protective effects. We hypothesized that short-term statin therapy may have beneficial effects in patients with nonischemic heart failure.

Methods and Results— Sixty-three patients with symptomatic, nonischemic, dilated cardiomyopathy were randomly divided into 2 groups. One group received simvastatin (n=24), and the other group received placebo (n=27). The initial dose of simvastatin was 5 mg/d, which was increased to 10 mg/d after 4 weeks. After 14 weeks, patients receiving simvastatin exhibited a modest reduction in serum cholesterol level compared with patients receiving placebo (130±13 versus 148±18, P<0.05). Patients treated with simvastatin had a lower New York Heart Association functional class compared with patients receiving placebo (2.04±0.06 versus 2.32±0.05, P<0.01). This corresponded to improved left ventricular ejection fraction in the simvastatin group (34±3 to 41±4%, P<0.05) but not in the placebo group. Furthermore, plasma concentrations of tumor necrosis factor-{alpha}, interleukin-6, and brain natriuretic peptide were significantly lower in the simvastatin group compared with the placebo group.

Conclusions— Short-term statin therapy improves cardiac function, neurohormonal imbalance, and symptoms associated with idiopathic dilated cardiomyopathy. These findings suggest that statins may have therapeutic benefits in patients with heart failure irrespective of serum cholesterol levels or atherosclerotic heart disease.


Key Words: heart failure • statins • cholesterol • endothelium • inflammation




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J. Am. Coll. Cardiol., January 17, 2006; 47(2): 332 - 337.
[Abstract] [Full Text] [PDF]


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Home page
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[Abstract] [Full Text] [PDF]


Home page
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J. Am. Coll. Cardiol., June 21, 2005; 45(12): 2078 - 2087.
[Abstract] [Full Text] [PDF]


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Home page
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Circulation, May 10, 2005; 111(18): 2356 - 2363.
[Abstract] [Full Text] [PDF]


Home page
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K. O'Neil-Callahan, G. Katsimaglis, M. R. Tepper, J. Ryan, C. Mosby, J. P.A. Ioannidis, and P. G. Danias
Statins decrease perioperative cardiac complications in patients undergoing noncardiac vascular surgery: The Statins for Risk Reduction in Surgery (StaRRS) study
J. Am. Coll. Cardiol., February 1, 2005; 45(3): 336 - 342.
[Abstract] [Full Text] [PDF]


Home page
Arch Intern MedHome page
J. G. Ray, Y. Gong, K. Sykora, and J. V. Tu
Statin Use and Survival Outcomes in Elderly Patients With Heart Failure
Arch Intern Med, January 10, 2005; 165(1): 62 - 67.
[Abstract] [Full Text] [PDF]


Home page
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HMG-CoA reductase inhibitor attenuates experimental autoimmune myocarditis through inhibition of T cell activation
Cardiovasc Res, December 1, 2004; 64(3): 412 - 420.
[Abstract] [Full Text] [PDF]


Home page
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K. E. Porter, N. A. Turner, D. J. O'Regan, and S. G. Ball
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Cardiovasc Res, December 1, 2004; 64(3): 507 - 515.
[Abstract] [Full Text] [PDF]


Home page
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Cardiomyocyte-Restricted Overexpression of Endothelial Nitric Oxide Synthase (NOS3) Attenuates {beta}-Adrenergic Stimulation and Reinforces Vagal Inhibition of Cardiac Contraction
Circulation, October 26, 2004; 110(17): 2666 - 2672.
[Abstract] [Full Text] [PDF]


Home page
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Circulation, October 5, 2004; 110(14): 1933 - 1939.
[Abstract] [Full Text] [PDF]


Home page
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Statins Are Associated With a Reduced Incidence of Perioperative Mortality After Coronary Artery Bypass Graft Surgery
Circulation, September 14, 2004; 110(11_suppl_1): II-45 - II-49.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
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Statins Inhibit {beta}-Adrenergic Receptor-Stimulated Apoptosis in Adult Rat Ventricular Myocytes via a Rac1-Dependent Mechanism
Circulation, July 27, 2004; 110(4): 412 - 418.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
A. E. Tsirka, K. Trinkaus, S.-C. Chen, S. E. Lipshultz, J. A. Towbin, S. D. Colan, V. Exil, A. W. Strauss, and C. E. Canter
Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation
J. Am. Coll. Cardiol., July 21, 2004; 44(2): 391 - 397.
[Abstract] [Full Text] [PDF]


Home page
JAMAHome page
F. M. Sacks
High-Intensity Statin Treatment for Coronary Heart Disease
JAMA, March 3, 2004; 291(9): 1132 - 1134.
[Full Text] [PDF]


Home page
Eur Heart J SupplHome page
F.M Sacks
Do statins play a role in the early management of the acute coronary syndrome?
Eur. Heart J. Suppl., March 1, 2004; 6(suppl_A): A32 - A36.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
P. van der Harst, A. A. Voors, D. J. van Veldhuisen, J. K. Liao, K. Node, M. Fujita, M. Hori, and M. Kitakaze
Short-Term Statin Therapy and Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy * Response
Circulation, February 10, 2004; 109 (5): e34 - e34.
[Full Text] [PDF]