Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group
BF Uretsky,
JB Young,
FE Shahidi,
LG Yellen,
MC Harrison,
and
MK Jolly
Presbyterian University Hospital, Pittsburgh, Pennsylvania 15213.
OBJECTIVES. The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure. BACKGROUND. Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy. METHODS. Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin. RESULTS. Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016). CONCLUSIONS. These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.
This article has been cited by other articles:
|
|
|
|
 
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
e1 - e90.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, M. A. Silver, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
1343 - 1382.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
1977 - 2016.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
e391 - e479.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland and D. Cullington
Digoxin: Quo Vadis?
Circ Heart Fail,
March 1, 2009;
2(2):
81 - 85.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. V. Georgiopoulou, A. P. Kalogeropoulos, G. Giamouzis, S. A. Agha, M. A. Rashad, S. Waheed, S. Laskar, A. L. Smith, and J. Butler
Digoxin Therapy Does Not Improve Outcomes in Patients With Advanced Heart Failure on Contemporary Medical Therapy
Circ Heart Fail,
March 1, 2009;
2(2):
90 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ratain, T. Eisen, W. M. Stadler, K. T. Flaherty, S. B. Kaye, G. L. Rosner, M. Gore, A. A. Desai, A. Patnaik, H. Q. Xiong, et al.
Phase II Placebo-Controlled Randomized Discontinuation Trial of Sorafenib in Patients With Metastatic Renal Cell Carcinoma
J. Clin. Oncol.,
June 1, 2006;
24(16):
2505 - 2512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gheorghiade, D. J. van Veldhuisen, and W. S. Colucci
Contemporary Use of Digoxin in the Management of Cardiovascular Disorders
Circulation,
May 30, 2006;
113(21):
2556 - 2564.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ahmed, M. W. Rich, T. E. Love, D. M. Lloyd-Jones, I. B. Aban, W. S. Colucci, K. F. Adams, and M. Gheorghiade
Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial
Eur. Heart J.,
January 2, 2006;
27(2):
178 - 186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Young
Whither Withering's Legacy?: Digoxin's Role in Our Contemporary Pharmacopeia for Heart Failure
J. Am. Coll. Cardiol.,
August 2, 2005;
46(3):
505 - 507.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. G. Olsson, K. Swedberg, A. L. Clark, K. K. Witte, and J. G.F. Cleland
Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review
Eur. Heart J.,
April 2, 2005;
26(8):
778 - 793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Burger and H. B.-L. Rocca
Pharmacotherapy of Congestive Heart Failure in Elderly Patients
Journal of Cardiovascular Pharmacology and Therapeutics,
April 1, 2005;
10(2):
85 - 94.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. T. Yan, R. T. Yan, and P. P. Liu
Narrative Review: Pharmacotherapy for Chronic Heart Failure: Evidence from Recent Clinical Trials
Ann Intern Med,
January 18, 2005;
142(2):
132 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. E Cayley Jr
Digoxin in chronic heart failure
Fam. Pract.,
August 1, 2004;
21(4):
469 - 472.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Rahimtoola
Digitalis Therapy for Patients in Clinical Heart Failure
Circulation,
June 22, 2004;
109(24):
2942 - 2946.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gheorghiade, K. F. Adams Jr, and W. S. Colucci
Digoxin in the Management of Cardiovascular Disorders
Circulation,
June 22, 2004;
109(24):
2959 - 2964.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Chutka, P. Y. Takahashi, and R. W. Hoel
Inappropriate Medications for Elderly Patients
Mayo Clin. Proc.,
January 1, 2004;
79(1):
122 - 139.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D B McKenzie and A J Cowley
Drug therapy in chronic heart failure
Postgrad. Med. J.,
November 1, 2003;
79(937):
634 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Petrie
It cannot be cardiac failure because the heart is not enlarged on the chest X-ray
Eur J Heart Fail,
March 1, 2003;
5(2):
117 - 119.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Radzewitz, E. Miche, G. Herrmann, M. Nowak, U. Montanus, U. Adam, Y. Stockmann, and M. Barth
Exercise and muscle strength training and their effect on quality of life in patients with chronic heart failure
Eur J Heart Fail,
October 1, 2002;
4(5):
627 - 634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K Kjeldsen, A Norgaard, and M Gheorghiade
Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure
Cardiovasc Res,
September 1, 2002;
55(4):
710 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B Swynghedauw and D Charlemagne
What is wrong with positive inotropic drugs? Lessons from basic science and clinical trials
Eur. Heart J. Suppl.,
April 1, 2002;
4(suppl_D):
D43 - D49.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. F. Adams Jr, M. Gheorghiade, B. F. Uretsky, J. H. Patterson, T. A. Schwartz, and J. B. Young
Clinical benefits of low serum digoxin concentrations in heart failure
J. Am. Coll. Cardiol.,
March 20, 2002;
39(6):
946 - 953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. van Veldhuisen
Low-dose digoxin in patients with heart failure: Less toxic and at least as effective?
J. Am. Coll. Cardiol.,
March 20, 2002;
39(6):
954 - 956.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ahmed, R. M. Allman, and J. F. DeLong
Inappropriate Use of Digoxin in Older Hospitalized Heart Failure Patients
J. Gerontol. A Biol. Sci. Med. Sci.,
February 1, 2002;
57(2):
M138 - 143.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M.C. Petrie, C. Berry, S. Stewart, and J.J.V. McMurray
Failing ageing hearts
Eur. Heart J.,
November 1, 2001;
22(21):
1978 - 1990.
[PDF]
|
|
|
|
|
|
|
J. G F Cleland, J. John, J. Dhawan, and A. Clark
What is the optimal medical management of ischaemic heart failure?
Br. Med. Bull.,
October 1, 2001;
59(1):
135 - 158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Hassapoyannes, B. M. Easterling, K. Chavda, K. K. Chavda, M. R. Movahed, and G. W. Welch
The effect of chronic digitalization on pump function in systolic heart failure
Eur J Heart Fail,
October 1, 2001;
3(5):
593 - 599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Rich, F. McSherry, W. O. Williford, S. Yusuf, and for the Digitalis Investigation Group
Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study
J. Am. Coll. Cardiol.,
September 1, 2001;
38(3):
806 - 813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ratain, W. M. Stadler, E. L. Korn, S. G. Arbuck, J. M. Pluda, R. Simon, R. S. Kaplan, and M. C. Christian
Clinical Trial Designs for Cytostatic Agents
J. Clin. Oncol.,
June 15, 2001;
19(12):
3154 - 3155.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Opasich, G.D Pinna, A Mazza, O Febo, R Riccardi, P.G Riccardi, S Capomolla, G Forni, F Cobelli, and L Tavazzi
Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice?
Eur. Heart J.,
March 2, 2001;
22(6):
488 - 496.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Gomberg-Maitland, D. A. Baran, and V. Fuster
Treatment of Congestive Heart Failure: Guidelines for the Primary Care Physician and the Heart Failure Specialist
Arch Intern Med,
February 12, 2001;
161(3):
342 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. W. Stevenson and R. L. Kormos
Mechanical cardiac support 2000: current applications and future trial design: June 15-16, 2000 Bethesda, Maryland
J. Am. Coll. Cardiol.,
January 1, 2001;
37(1):
340 - 370.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J.F. Holubarsch, W. S. Colucci, T. Meinertz, W. Gaus, and M. Tendera
Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in congestive heart failure (SPICE) -- rationale, study design and study protocol
Eur J Heart Fail,
December 1, 2000;
2(4):
431 - 437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lonn and R. McKelvie
Regular review: Drug treatment in heart failure
BMJ,
April 29, 2000;
320(7243):
1188 - 1192.
[Full Text]
|
|
|
|
|
|
|
H. M. Krumholz, D. W. Baker, C. M. Ashton, S. B. Dunbar, G. C. Friesinger, E. P. Havranek, M. A. Hlatky, M. Konstam, D. L. Ordin, I. L. Pina, et al.
Evaluating Quality of Care for Patients With Heart Failure
Circulation,
March 28, 2000;
101
(12):
e122 - e140.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Rich and R. F. Nease
Cost-effectiveness Analysis in Clinical Practice: The Case of Heart Failure
Arch Intern Med,
August 9, 1999;
159(15):
1690 - 1700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guyatt
A 75-Year-Old Man With Congestive Heart Failure
JAMA,
June 23, 1999;
281(24):
2321 - 2328.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Petrie, N. F. Dawson, D. R. Murdoch, A. P. Davie, and J. J. V. McMurray
Failure of Women's Hearts
Circulation,
May 4, 1999;
99(17):
2334 - 2341.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Williamson, K. A. Thrasher, K. B. Fulton, N. M. A. LaPointe, G. D. Dunham, A. A. Cooper, P. S. Barrett, and J. H. Patterson
Digoxin Toxicity: An Evaluation in Current Clinical Practice
Arch Intern Med,
December 1, 1998;
158(22):
2444 - 2449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Young, M. Gheorghiade, B. F. Uretsky, J. H. Patterson, and K. F. Adams Jr.
Superiority of "triple" drug therapy in heart failure: insights from the PROVED and RADIANCE trials
J. Am. Coll. Cardiol.,
September 1, 1998;
32(3):
686 - 692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. T. Abraham
Pharmacologic Management of Chronic Heart Failure: A Review
Seminars in Cardiothoracic and Vascular Anesthesia,
September 1, 1998;
2(3):
168 - 190.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. A Schmidt and K. Kjeldsen
Human myocardial Na,K-ATPase -- quantification, regulation and relation to Ca
Cardiovasc Res,
February 1, 1998;
37(2):
335 - 345.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Sullebarger, P. M. D'Ambra, L. C. Clark, L. Thanikarry, and H. L. Fontanet
Effect of Digoxin on Ventricular Remodeling and Responsiveness of {beta}-Adrenoceptors in Chronic Volume Overload
Journal of Cardiovascular Pharmacology and Therapeutics,
January 1, 1998;
3(4):
281 - 290.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K Pardaens, J Van Cleemput, J Vanhaecke, and R H Fagard
Atrial fibrillation is associated with a lower exercise capacity in male chronic heart failure patients
Heart,
December 1, 1997;
78(6):
564 - 568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Matsumori, K. Ono, R. Nishio, H. Igata, B Pharm, T. Shioi, S. Matsui, Y. Furukawa, A. Iwasaki, Y. Nose, et al.
Modulation of Cytokine Production and Protection Against Lethal Endotoxemia by the Cardiac Glycoside Ouabain
Circulation,
September 2, 1997;
96(5):
1501 - 1506.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
The Digitalis Investigation Group
The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure
N. Engl. J. Med.,
February 20, 1997;
336(8):
525 - 533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Packer
End of the Oldest Controversy in Medicine -- Are We Ready to Conclude the Debate on Digitalis?
N. Engl. J. Med.,
February 20, 1997;
336(8):
575 - 576.
[Full Text]
|
|
|
|
|
|
|
K. Ogunyankin and B. N. Singh
Reflections on Recent Clinical Trials in Patients With Heart Failure and Those With Reduced Ventricular Function
Journal of Cardiovascular Pharmacology and Therapeutics,
January 1, 1997;
2(3):
147 - 152.
[PDF]
|
|
|
|
|
|
|
M. R. Costanzo, S. Augustine, R. Bourge, M. Bristow, J. B. O'Connell, D. Driscoll, and E. Rose
Selection and Treatment of Candidates for Heart Transplantation : A Statement for Health Professionals From the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association
Circulation,
December 15, 1995;
92(12):
3593 - 3612.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
COMMITTEE MEMBERS, J. F. WILLIAMS Jr, M. R. BRISTOW, M. B. FOWLER, G. S. FRANCIS, A. GARSON Jr, B. J. GERSH, D. F. HAMMER, M. A. HLATKY, C. V. LEIER, et al.
Guidelines for the Evaluation and Management of Heart Failure : Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure)
Circulation,
November 1, 1995;
92(9):
2764 - 2784.
[Full Text]
|
|
|
|
|
|
|
M. Gheorghiade, V. B. Hall, G. Jacobsen, M. Alam, H. Rosman, and S. Goldstein
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,
October 1, 1995;
92(7):
1801 - 1807.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Zoneraich and D. H. Spodick
Bedside Science Reduces Laboratory Art : Appropriate Use of Physical Findings to Reduce Reliance on Sophisticated and Expensive Methods
Circulation,
April 1, 1995;
91(7):
2089 - 2092.
[Full Text]
|
|
|
|
|
|
|
J. McMurray and A. Rankin
Recent Advances: Cardiology II: Treatment of heart failure and atrial fibrillation and arrhythmias
BMJ,
December 17, 1994;
309(6969):
1631 - 1635.
[Full Text]
|
|
|
|
|
|
|
W. W. Parmley
Clinical Practice Guidelines: Does the Cookbook Have Enough Recipes?
JAMA,
November 2, 1994;
272(17):
1374 - 1375.
[Abstract]
[PDF]
|
|
|
|
|
|
|
MORE EVIDENCE THAT DIGOXIN IS BENEFICIAL FOR CHF
Journal Watch (General),
October 8, 1993;
1993(1008):
4 - 4.
[Full Text]
|
|
|
|
