Information de reference pour ce titreAccession Number: | 00005407-200302190-00036.
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Author: | Rathore, Saif S. MPH; Curtis, Jeptha P. MD; Wang, Yongfei MS; Bristow, Michael R. MD, PhD; Krumholz, Harlan M. MD, SM
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Institution: | The Section of Cardiovascular Medicine (Messrs Rathore and Wang and Drs Curtis and Krumholz), Department of Internal Medicine and the Section of Health Policy and Administration (Dr Krumholz), Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn; Division of Cardiology, University of Colorado Health Sciences Center, Denver (Dr Bristow); and the Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Conn (Dr Krumholz).
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Title: | |
Source: | JAMA. 289(7):871-878, February 19, 2003.
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Abstract: | Context: The Digitalis Investigation Group (DIG) trial reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function. The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed.
Objective: To assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure.
Design, Setting, and Patients: Post hoc analysis of the randomized, double-blinded, placebo-controlled DIG trial, conducted from August 1991 to December 1995, with the main analysis restricted to men with a left ventricular ejection fraction of 45% or less (n = 3782). Patients randomly assigned to receive digoxin were divided into 3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n = 322; and >=1.2 ng/mL, n = 277) and compared with patients randomly assigned to receive placebo (n = 2611).
Main Outcome Measure: All-cause mortality at a mean follow-up of 37 months.
Results: Higher SDCs were associated with increased crude all-cause mortality rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and >=1.2 ng/mL, 48.0%; P = .006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate compared with patients receiving placebo. Digoxin was not associated with a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6% increase; 95% CI, - 3.0% to 8.3%), whereas patients with SDCs of 1.2 ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality rate than patients receiving placebo. The association between SDC and mortality persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR] 0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC >=1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo).
Conclusions: Our findings demonstrate that higher SDCs were associated with increased mortality and suggest that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.
Copyright 2003 by the American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use. American Medical Association, 515 N. State St, Chicago, IL 60610.
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Author Keywords: | Digoxin; Heart Failure, Congestive; Left Ventricular Dysfunction; Men; Mortality; Randomized Trials; Ventricular Dysfunction, Left.
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References: | 1. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525-533.
2. The Digitalis Investigation Group. Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: a large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure. Control Clin Trials. 1996;17:77-97.
3. Terra SG, Washam JB, Dunham GD, Gattis WA. Therapeutic range of digoxin's efficacy in heart failure: what is the evidence? Pharmacotherapy. 1999;19:1123-1126.
4. Gheorghiade M, Hall VB, Jacobsen G, Alam M, Rosman H, Goldstein S. Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. Circulation. 1995;92:1801-1807.
5. Slatton ML, Irani WN, Hall SA, et al. Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? J Am Coll Cardiol. 1997;29:1206-1213.
6. Ware JA, Snow E, Luchi JM, Luchi RJ. Effect of digoxin on ejection fraction in elderly patients with heart failure. J Am Geriatr Soc. 1984;32:631-635.
7. Adams KFJ, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB. Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol. 2002;39:946-953.
8. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Available at: http://www.acc.org/clinical/guid...- ouverture dans une nouvelle fenêtre. Accessed January 17, 2003.
9. Bristow MR, Port JD, Kelly RA. Treatment of heart failure: pharmacological methods. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease. 6th ed. Philadelphia, Pa: WB Saunders; 2001.
10. LeJemtel TH, Sonnenblick EH, Frishman WH. Diagnosis and management of heart failure. In: Fuster V, Alexander RW, O'Rourke RA, eds. Hurst's The Heart. 10th ed. New York, NY: McGraw-Hill; 2001.
11. van Veldhuisen DJ. Low-dose digoxin in patients with heart failure: less toxic and at least as effective? J Am Coll Cardiol. 2002;39:954-956.
12. Jelliffe RW, Brooker G. A nomogram for digoxin therapy. Am J Med. 1974;57:63-68.
13. Rathore SS, Wang Y, Krumholz HM. Sex differences in digoxin efficacy in the treatment of heart failure. N Engl J Med. 2002;347:1403-1411.
14. Estimation of GFR Am J Kidney Dis. 2002;39:S76-S110.
15. Royston P, Altman DG. Regression using fractional polynomials of continuous variables: parsimonious parametric modeling. Appl Stat. 1994;43:429-467.
16. Gibbs CR, Davies MK, Lip GY. ABC of heart failure: management: digoxin and other inotropes, beta blockers, and antiarrhythmic and antithrombotic treatment. BMJ. 2000;320:495-498.
17. Jahangir A. Digoxin. In: Murphy JG, ed. Mayo Clinic Cardiology Review. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000.
18. Liu P, Arnold M, Belenkie I, et al. The 2001 Canadian Cardiovascular Society consensus guideline for the management and prevention of heart failure. Can J Cardiol. 2001;17:5E-25E.
19. Soto J, Avendano C, Vilchez FG. Digoxin in patients with heart failure [letter]. N Engl J Med. 1997;337:129.
20. Hauptman PJ, Kelly RA. Digitalis. Circulation. 1999;99:1265-1270.
21. Gheorghiade M, Pitt B. Digitalis Investigation Group (DIG) trial: a stimulus for further research. Am Heart J. 1997;134:3-12.
22. Gheorghiade M, Ferguson D. Digoxin: a neurohormonal modulator in heart failure? Circulation. 1991;84:2181-2186.
23. Newton GE, Tong JH, Schofield AM, Baines AD, Floras JS, Parker JD. Digoxin reduces cardiac sympathetic activity in severe congestive heart failure. J Am Coll Cardiol. 1996;28:155-161.
24. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol. 1992;20:248-254.
25. Packer M. The development of positive inotropic agents for chronic heart failure: how have we gone astray. J Am Coll Cardiol. 1993;22:119A-126A.
26. Remme WJ. Inotropic agents for heart failure: what if digoxin increases mortality? Br Heart J. 1994;72:S92-S99.
27. Mancini DM, Benotti JR, Elkayam U, et al. Antiarrhythmic drug use and high serum levels of digoxin are independent adverse prognostic factors in patients with chronic heart failure [abstract]. Circulation. 1991;84:II-243.
28. Ordog GJ, Benaron S, Bhasin V, Wasserberger J, Balasubramanium S. Serum digoxin levels and mortality in 5,100 patients. Ann Emerg Med. 1987;16:32-39.
29. Leor J, Goldbourt U, Rabinowitz B, et al. Digoxin and increased mortality among patients recovering from acute myocardial infarction: importance of digoxin dose. Cardiovasc Drugs Ther. 1995;9:723-729.
30. Cohn JN, Goldstein SO, Greenberg BH, et al. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl J Med. 1998;339:1810-1816.
31. van Veldhuisen DJ, Veld AJM, Dunselman PHJM, et al. Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DMIT). J Am Coll Cardiol. 1993;22:1564-1573.
32. Lowes BD, Higginbotham M, Petrovich L, et al. Low-dose enoximone improves exercise capacity in chronic heart failure. J Am Coll Cardiol. 2000;36:501-508.
33. Bristow MR, Lowes BD. Low-dose inotropic therapy for ambulatory heart failure. Coron Artery Dis. 1994;5:112-118.
34. Krohn BG. Controlling the effectiveness of digoxin [letter]. J Am Coll Cardiol. 2002;40:836.
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Language: | English.
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Document Type: | Original Contribution.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0098-7484
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NLM Journal Code: | 7501160
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