Published Online
on January 29, 2007

A more recent version of this article appeared on February 6, 2007

This Article Full Text (PDF) CME: Take the course for this article: Circulation: February 6, 2007, Volume 115, Number 5 All Versions of this Article: 115/5/576    most recent CIRCULATIONAHA.106.625574v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khush, K. K. Articles by Wenger, N. K. Search for Related Content PubMed PubMed Citation Articles by Khush, K. K. Articles by Wenger, N. K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ATORVASTATIN HEPTANOIC ACID PYRROLE Medline Plus Health Information Heart Failure Related Collections Congestive Lipids Chronic ischemic heart disease

Submitted on March 8, 2006
Accepted on November 3, 2006

Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure. Subgroup Analysis of the Treating to New Targets (TNT) Study

Kiran K. Khush MD, David D. Waters MD^*, Vera Bittner MD, Prakash C. Deedwania MD, John J.P. Kastelein MD, Sandra J. Lewis MD, and Nanette K. Wenger MD

From the Divisions of Cardiology, University of California, San Francisco School of Medicine, San Francisco, Calif (K.K.K., D.D.W.); Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham (V.B.); UCSF School of Medicine, Fresno, Calif (P.C.D.); Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (J.J.P.K.); Portland Cardiovascular Institute, Portland, Ore (S.J.L.); and Emory University School of Medicine, Atlanta, Ga (N.K.W.).

^* To whom correspondence should be addressed. E-mail: dwaters{at}medsfgh.ucsf.edu.

Background--Statins reduce the rate of major cardiovascular events in high-risk patients, but their potential benefit as treatment for heart failure (HF) is less clear.

Methods and Results--Patients (n=10 001) with stable coronary disease were randomized to treatment with atorvastatin 80 or 10 mg/d and followed up for a median of 4.9 years. A history of HF was present in 7.8% of patients. A known ejection fraction <30% and advanced HF were exclusion criteria for the study. A predefined secondary end point of the study was hospitalization for HF. The incidence of hospitalization for HF was 2.4% in the 80-mg arm and 3.3% in the 10-mg arm (hazard ratio, 0.74; 95% confidence interval, 0.59 to 0.94; P=0.0116). The treatment effect of the higher dose was more marked in patients with a history of HF: 17.3% versus 10.6% in the 10- and 80-mg arms, respectively (hazard ratio, 0.59; 95% confidence interval, 0.4 to 0.88; P=0.009). Among patients without a history of HF, the rates of hospitalization for HF were much lower: 1.8% in the 80-mg group and 2.0% in the 10-mg group (hazard ratio, 0.87; 95% confidence interval, 0.64 to 1.16; P=0.34). Only one third of patients hospitalized for HF had evidence of preceding angina or myocardial infarction during the study period. Blood pressure was almost identical during follow-up in the treatment groups.

Conclusions--Compared with a lower dose, intensive treatment with atorvastatin in patients with stable coronary disease significantly reduces hospitalizations for HF. In a post hoc analysis, this benefit was observed only in patients with a history of HF. The mechanism accounting for this benefit is unlikely to be due primarily to a reduction in interim coronary events or differences in blood pressure.

Key words: atorvastatin • cholesterol • coronary disease • heart failure • hospitalizations • lipids • statins

This article has been cited by other articles:

				J. G. Cleland, J. J.V. McMurray, J. Kjekshus, J. H. Cornel, P. Dunselman, C. Fonseca, A. Hjalmarson, J. Korewicki, M. Lindberg, N. Ranjith, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J. Am. Coll. Cardiol., November 10, 2009; 54(20): 1850 - 1859. [Abstract] [Full Text] [PDF]

				J. G.F. Cleland, A. P. Coletta, A. L. Clark, and D. Cullington Clinical trials update from the American College of Cardiology 2009: ADMIRE-HF, PRIMA, STICH, REVERSE, IRIS, partial ventricular support, FIX-HF-5, vagal stimulation, REVIVAL-3, pre-RELAX-AHF, ACTIVE-A, HF-ACTION, JUPITER, AURORA, and OMEGA Eur J Heart Fail, June 1, 2009; 11(6): 622 - 630. [Abstract] [Full Text] [PDF]

				U. Landmesser, K. C. Wollert, and H. Drexler Potential novel pharmacological therapies for myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 519 - 527. [Abstract] [Full Text] [PDF]

				E. D. Pagourelias, C. Koumaras, A. I. Kakafika, K. Tziomalos, P. G. Zorou, V. G. Athyros, and A. Karagiannis Cardiorenal Anemia Syndrome: Do Erythropoietin and Iron Therapy Have a Place in the Treatment of Heart Failure? Angiology, February 1, 2009; 60(1): 74 - 81. [Abstract] [PDF]

				B. M. Scirica, C. P. Cannon, M. S. Sabatine, P. Jarolim, S. Sloane, N. Rifai, E. Braunwald, D. A. Morrow, and for the PROVE IT-TIMI 22 Investigators Concentrations of C-Reactive Protein and B-Type Natriuretic Peptide 30 Days after Acute Coronary Syndromes Independently Predict Hospitalization for Heart Failure and Cardiovascular Death Clin. Chem., February 1, 2009; 55(2): 265 - 273. [Abstract] [Full Text] [PDF]

				A. P. Coletta, D. Cullington, A. L. Clark, and J. G.F. Cleland Clinical trials update from European Society of Cardiology meeting 2008: TIME-CHF, BACH, BEAUTIFUL, GISSI-HF, and HOME-HF Eur J Heart Fail, December 1, 2008; 10(12): 1264 - 1267. [Abstract] [Full Text] [PDF]

				J. H. O'Keefe, K. A. Bybee, and C. J. Lavie Intensive Lipid Intervention in the Post-ENHANCE Era Mayo Clin. Proc., August 1, 2008; 83(8): 867 - 869. [Full Text] [PDF]

				V. G. Athyros, A. I. Kakafika, K. Tziomalos, A. Karagiannis, and D. P. Mikhailidis CORONA, Statins, and Heart Failure: Who Lost the Crown? Angiology, March 1, 2008; 59(1): 5 - 8. [PDF]

				J. G.F. Cleland, A. P. Coletta, A. T. Abdellah, D. Cullington, A. L. Clark, and A. S. Rigby Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy Eur J Heart Fail, January 1, 2008; 10(1): 102 - 108. [Abstract] [Full Text] [PDF]