Hospital Pharmacy - December 2019 - 352

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Hospital Pharmacy 54(6)

administration. The onset of diuresis seen with MTZ and
CTZ is 1 hour versus 15 minutes, respectively.9,10
Several studies have sought to end this debate, with a
recent retrospective cohort study showing similar efficacy
between the agents in net urine output (UOP); however, the
study had significant limitations. Due to the small sample
size (55 patients), inclusion of patients with heart failure
with preserved ejection fraction (HFpEF), inclusion of only
patients with creatinine clearance of 15 to 50 mL/min, and
use of net UOP as the primary outcome, further investigation
is needed to determine whether a difference exists between
MTZ and CTZ for this indication.11 Another recent retrospective study by Shulenberger et al compared MTZ and
CTZ in 177 patients with ADHF resistant to loop diuretics.
No difference in the primary outcome of change in 24-hour
net UOP was seen; however, this study was similarly limited
by inclusion of HFpEF patients and use of net UOP as the
primary outcome which can be drastically affected by oral
intake.12 The purpose of the present study is to determine
whether CTZ increases change in 24-hour total UOP more
effectively than MTZ in patients with ADHF and reduced
ejection fraction (EF) receiving IV loop diuretics.

(COT) total UOP, 24-hour net UOP, and COT net UOP.
Total UOP is the total UOP without fluid intake subtracted,
net UOP is the total UOP with fluid intake subtracted, baseline UOP is the sum of the UOP occurring in the 24 hours
prior to the first dose, 24-hour values are the sum of the UOP
at 24 hours after initiation, and COT is the sum of UOP at the
completion of the consecutive COT. Secondary safety endpoints include hypokalemia (serum potassium <3.3 mEq/L),
hyperkalemia (serum potassium >4.9 mEq/L), hyponatremia
(serum sodium <135 mEq/L), hypernatremia (serum sodium
>145 mEq/L), hypochloremia (serum chloride <97 mEq/L),
hyperchloremia (serum chloride >110 mEq/L), hypocalcemia (corrected calcium <8.5 mg/dL), hypercalcemia (corrected calcium >10.3 mg/dL), hypomagnesemia (serum
magnesium <1.4 mg/dL), hypermagnesemia (serum magnesium >2.5 mg/dL), and adverse effects such as hypotension
(systolic blood pressure [SBP] <90 mm Hg), agranulocytosis
(ANC <100 cells/mm3), and pancreatitis (lipase >300
units/L). Laboratory data were assessed from first dose of
thiazide diuretic through 48 hours following the final dose.
Adverse effects were only recorded if they were not present
prior to thiazide administration.

Methods

Statistical Analysis

Study Design

All comparisons of baseline and outcomes data were
unpaired, and all tests of significance were two-tailed.
Continuous variables were compared using the Student's t
test for normally distributed data and the Mann-Whitney U
test for nonnormally distributed data. The chi-squared or
Fisher exact test was used to compare categorical variables.
A statistical software program (SPSS, version 18.0 for
Windows; SPSS, Inc; Chicago, Illinois) was used to perform
the analyses. A P value of <.05 was considered significant.
The subgroup analysis evaluating clinical outcomes in ICU
patients receiving vasopressors was determined a priori.

This study was a retrospective chart review conducted at
Barnes-Jewish Hospital, St. Louis, Missouri, from September
1, 2013, to August 15, 2016. The study was approved by the
Washington University at St. Louis Institutional Review
Board. Hospitalized adult patients (age ⩾18 years old) with
a primary diagnosis of ADHF, EF ⩽40%, receiving at least
one dose of either MTZ ⩾5 mg or CTZ ⩾500 mg in addition
to IV loop diuretics were included in the study. Inclusion criteria required UOP data and IV loop diuretic utilization 24
hours prior to the first dose and 24 hours after the last dose of
a thiazide diuretic. Patients were excluded if they were
receiving dialysis, ultrafiltration, vasopressin antagonists,
only IV medications, had a left ventricular assist device
(LVAD), cirrhosis, albumin <2.5 mg/dL, anuria, allergy to
study drugs, or received both MTZ and CTZ. An a priori
subgroup analysis was also conducted which included all
patients in the study who were admitted to an intensive care
unit (ICU) and receiving a vasopressor at the time of thiazide
diuretic administration. Patients were identified using the
medical informatics database at Barnes-Jewish Hospital.
Data were collected from the medical informatics database
query and by manual chart review.

Endpoints
The primary efficacy endpoint was the change in 24-hour
total UOP following the addition of thiazide. The secondary
efficacy endpoints were 24-hour total UOP, course of therapy

Results
Patient Groups and Clinical Characteristics
During the study period of 3 years, 1002 patients were admitted to Barnes-Jewish Hospital for ADHF. After patient exclusions, 168 patients were included, 60 receiving MTZ ⩾5 mg,
and 108 receiving CTZ ⩾500 mg (Figure 1). The most common exclusion criteria were HFpEF, IV loop diuretic use for
<24 hours prior to addition of thiazide, and receiving both
MTZ and CTZ during the hospitalization.
Baseline characteristics were similar between the two
groups (Table 1). The majority of patients were Caucasian
men with an age of 64 years and an EF of 22%. All patients
were receiving at least 80 mg IV furosemide (or equivalent)
prior to the addition of thiazide diuretics. There were no statistically significant differences in median B-type natriuretic
peptide (BNP) (1371 pg/mL CTZ vs 1516.5 pg/mL MTZ,

Hospital Pharmacy - December 2019

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