CLINICAL STUDIES
Superiority of "triple" drug therapy in heart failure: insights from the PROVED and RADIANCE trials
James B. Young, MD, FACC*,
Mihai Gheorghiade, MD, FACC ,
Barry F. Uretsky, MD, FACC ,
J. Herbert Patterson, PharmD and
Kirkwood F. Adams, Jr., MD, FACC||
* Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
Department of Medicine, Northwestern University Medical School, Evanston, Illinois, USA
Department of Medicine, University of Texas Medical Branch, Galveston, Texas, USA
|| Departments of Medicine and Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Manuscript received October 21, 1997;
revised manuscript received April 7, 1998,
accepted May 14, 1998.
Address for correspondence: Dr. Kirkwood F. Adams, Jr., Division of Cardiology, University of North Carolina at Chapel Hill, CB# 7075, Burnett-Womack Building, Chapel Hill, North Carolina 27599-7075
kfa{at}med.unc.edu
Objectives. We sought to study the efficacy of "triple" therapy with digoxin, diuretic and angiotensin-converting enzyme inhibitor (ACEI) compared to other combinations of these drugs in patients with symptomatic left ventricular systolic dysfunction.
Background. Controversy continues concerning the role of combining digoxin with diuretic and ACEI in the initial management of patients with heart failure.
Methods. The study utilized data from two studies of digoxin efficacy: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Worsening heart failure defined as augmentation of heart failure therapy or an emergency room visit or hospitalization for increased heart failure was the main outcome measure.
Results. A total of 266 patients comprising the four treatment groups of the combined PROVED (diuretic alone or digoxin and diuretic) and RADIANCE (ACEI and diuretic, or digoxin, diuretic and ACEI) trials were analyzed. Worsening heart failure occurred in only 4 of the 85 patients who continued digoxin, diuretic and ACEI therapy (4.7%) compared to 18 of the 42 patients (19%) on digoxin and diuretic therapy (p = 0.009), to 23 of the 93 patients (25%) on ACEI and diuretic therapy (p = 0.001) and to 18 of the 46 patients (39%) on diuretic alone (p < 0.001). Life table and multivariate analysis also demonstrated that worsening heart failure was least likely in patients treated with triple therapy (p < 0.01 vs. all other groups).
Conclusion. Pending definitive, prospective clinical trials, our results argue for triple therapy as the initial management of patients with symptomatic heart failure due to systolic dysfunction.
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Abbreviations and Acronyms
| | ACEI | = angiotensin-converting enzyme inhibitor | | DIG | = Digoxin Investigators Group | | PROVED | = Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin | | RADIANCE | = Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme |
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