Beruflich Dokumente
Kultur Dokumente
a
Colorado Cardiovascular Outcomes Research Group and Division of
Cardiology, University of Colorado Denver, Aurora, Colorado; bDivision
of Cardiology, University of Texas Southwestern, Dallas, Texas; cDuke
Clinical Research Institute and Division of Cardiology, Duke University
Medical Center, Durham, North Carolina; dSchool of Pharmacy, Campbell
University, Buies Creek, North Carolina; and eMomentum-Research, Inc.,
Durham, North Carolina. Manuscript received December 18, 2009; revised
manuscript received and accepted January 20, 2010.
*Corresponding author: Tel: 303-724-4713; fax: 303-724-2094.
E-mail address: larry.allen@ucdenver.edu (L.A. Allen).
0002-9149/10/$ see front matter 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2010.01.355
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Table 1
Baseline characteristics, stratified by treatment assignment
Variable
Age (years)
Black
Women
Diabetes mellitus
Hypertension
Atrial fibrillation
Coronary artery disease
Left ventricular ejection fraction (%)
Furosemide, home
Torsemide, home
Home oral furosemide equivalent (mg/24 h)
Thiazide or thiazide-type diuretic
Spironolactone
Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker
blocker
Systolic blood pressure (mm Hg)
Heart rate (beats/min)
Weight (kg)
Sodium (mEq)
Potassium (mEq)
Urea nitrogen (mg/dl)
Creatinine (mg/dl)
Glomerular filtration rate (ml/min/1.73 m2)
Hemoglobin (g/dl)
Twice Daily
(n 21)
Continuous
(n 20)
Data are expressed as mean SD (25th, 50th, and 75th percentiles) or as number (percentage).
Table 2
In-hospital outcome measures, stratified by treatment assignment
Variable
Furosemide dose (mg/24 h)
creatinine (mg/dl)
Urine output (ml)
weight (kg)
serum potassium (mEq/L)
Rates of hypokalemia (3.5 mEq/L)
serum sodium (mEq/L)
systolic blood pressure (mm Hg)
Length of stay (days)
Twice Daily
(n 21)
Continuous
(n 20)
p Value
162 48
160 (140 to 200)
0.02 0.39
0.1 (0.1 to 0.2)
5,113 2,258
4,675 (3,230 to 6,250)
1.64 2.34
2.55 (3.30 to 0.25)
0.07 0.57
0.2 (0.5 to 0.3)
5 (24%)
2.19 3.25
2 (5 to 0)
5.6 21.2
3 (15 to 7)
8.86 3.82
7 (5.5 to 11)
162 52
160 (120 to 240)
0.13 0.34
0.05 (0.05 to 0.35)
4,894 2,205
4,448 (3,625 to 4,650)
2.66 2.44
2.10 (4.85 to 1.25)
0.22 0.67
0.3 (0.2 to 0.7)
2 (10%)
1.15 3.12
1 (4 to 1)
2.9 15.0
0 (2 to 4)
9.85 11.72
7 (4.5 to 9.5)
1.00
0.18
0.64
0.27
0.08
0.44
0.30
0.11
0.69
Data are expressed as mean SD and as median (interquartile range). Measured from admission (hospital day 0) until hospital day 3 or discharge
(whichever came first), except for length of stay.
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0.3 mg/dl with power of 80%, assuming a standard deviation of 0.33 mg/dl and a 2-sided p value of 0.05.
Estimated glomerular filtration rate was calculated using
the Modification of Diet in Renal Disease (MDRD) equation.7 Torsemide was converted to furosemide equivalents
(torsemide 1 mg furosemide 2 mg). Analysis for all end
points was performed on an intention-to-treat basis. Comparisons of changes in outcomes from admission (hospital
day 0) to hospital day 3 (or discharge, whichever came first)
between the bolus and continuous arms were performed
using Wilcoxons rank-sum test for continuous variables
and the chi-square test for categorical variables. A 2-tailed
p value of 0.05 was used to determine significance. Analyses were conducted with SAS version 9.1 (SAS Institute
Inc., Cary, North Carolina).
Results
We enrolled and randomized 41 patients. For the overall
cohort, the mean age was 60 15 years, the mean ejection
fraction was 35 19%, and the mean estimated glomerular
filtration rate was 54 30 ml/min/1.73 m2. Mean oral home
dose of furosemide equivalent before admission was 99
108 mg/24 hours, with 29% (n 12) of patients taking no
loop diuretics before admission. Baseline characteristics
were not statistically different between arms except for
gender, which by random sampling produced fewer women
in the continuous infusion arm (p 0.005; Table 1).
Follow-up was 100% at discharge. There were no protocol violations, with all patients receiving furosemide dosing as dictated by study assignment starting 24 hours after
enrollment and continuing during the 48 hours after randomization. The mean doses of furosemide were similar
between arms over the first 48 hours (Table 2).
None of the outcomes showed a statistically significant
difference between bolus and continuous dosing from admission to hospital day 3 or discharge (Table 2). The primary
outcome of change in serum creatinine showed a nonsignificant trend toward improvement in the bolus dosing arm (Figure 1). The vector plot of urine output to change in creatinine
showed no significant relation between these 2 variables (Figure 2). Decreases in serum potassium, serum sodium, and
systolic blood pressure showed nonsignificant trends in favor
Figure 2. Vector end point of change in creatinine and urine output from
admission (hospital day 0) to hospital day 3 (or discharge if before day 3).
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