Comparative effectiveness of torasemide versus furosemide in symptomatic therapy in heart failure patients: Preliminary results from the randomized TORNADO trial

Abstract

BACKGROUND: Recent reports suggest that torasemide might be more beneficial than furosemide in patients with symptomatic heart failure (HF). The aim was to compare the effects of torasemide and furosemide on clinical outcomes in HF patients. METHODS: This study pilot consisted of data from the ongoing multicenter, randomized, unblinded endpoint phase IV TORNADO (NCT01942109) study. HF patients in New York Heart Association (NYHA) II–IV class with a stable dose of furosemide were randomized to treatment with equipotential dose of torasemide (4:1) or continuation of unchanged dose of furosemide. On enrollment and control visit (3 months after enrollment) clinical examination, 6-minute walk test (6MWT) and assessment of fluid retention by ZOE Fluid Status Monitor were performed. The primary endpoint was a composite of improvement of NYHA class, improvement of at least 50 m during 6MWT and decrease in fluid retention of at least 0.5 W after 3-months follow-up. RESULTS: The study group included 40 patients (median age 66 years; 77.5% male). During follow-up 7 patients were hospitalized for HF worsening (3 in torasemide and 4 in furosemide-treated patients). The primary endpoint reached 15 (94%) and 14 (58%) patients on torasemide and furosemide, respectively (p = 0.03). CONCLUSIONS: In HF patients treated with torasemide fluid overload and symptoms improved more than in the furosemide group. This positive effect occurred already within 3-month observation.

Full text

Address for correspondence: Michał Marchel, MD, PhD, 1st Department of Cardiology, Medical University of Warsaw,
ul. Banacha 1a, 02–097 Warszawa, Poland, tel: +48 22 599 29 58, e-mail: michal.marchel@wum.edu.pl
Received: 9.07.2019 Accepted: 23.11.2019
Comparative effectiveness of torasemide
versus furosemide in symptomatic therapy
in heart failure patients: Preliminary results
from the randomized TORNADO trial
Paweł Balsam1, Krzysztof Ozierański1, Michał Marchel1, Monika Gawałko1,
Łukasz Niedziela1, Agata Tymińska1, Bartosz Sieradzki1, Maciej Sieradzki1,
Anna Fojt1, Elwira Bakuła2, Renata Główczyńska1, Michał Peller1, Maciej Markulis1,
Janusz Bednarski2, Robert Kowalik1, Andrzej Cacko1, Grzegorz Niewiński3,
Krzysztof J. Filipiak1, Grzegorz Opolski1, Marcin Grabowski1
11st Chair and Department of Cardiology, Medical University of Warsaw, Poland
2Cardiology Unit, John Paul II Western Hospital, Grodzisk Mazowiecki, Poland
3Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland
Abstract
Background: Recent reports suggest that torasemide might be more benecial than furosemide in
patients with symptomatic heart failure (HF). The aim was to compare the effects of torasemide and
furosemide on clinical outcomes in HF patients.
Methods: This study pilot consisted of data from the ongoing multicenter, randomized, unblinded
endpoint phase IV TORNADO (NCT01942109) study. HF patients in New York Heart Association
(NYHA) II–IV class with a stable dose of furosemide were randomized to treatment with equipoten-
tial dose of torasemide (4:1) or continuation of unchanged dose of furosemide. On enrollment and
control visit (3 months after enrollment) clinical examination, 6-minute walk test (6MWT) and
assessment of uid retention by ZOE Fluid Status Monitor were performed. The primary endpoint was
a composite of improvement of NYHA class, improvement of at least 50 m during 6MWT and decrease
in uid retention of at least 0.5 W after 3-months follow-up.
Results: The study group included 40 patients (median age 66 years; 77.5% male). During follow-up
7 patients were hospitalized for HF worsening (3 in torasemide and 4 in furosemide-treated patients).
The primary endpoint reached 15 (94%) and 14 (58%) patients on torasemide and furosemide, respec-
tively (p = 0.03).
Conclusions: In HF patients treated with torasemide uid overload and symptoms improved more than
in the furosemide group. This positive effect occurred already within 3-month observation. (Cardiol J
2019; 26, 6: 661–668)
Key words: heart failure, hospitalization, loop diuretics, prognosis, symptoms
Introduction
Heart failure (HF) is one of the leading cardio-
vascular problems in Europe, with a prevalence of
1–2% in the adult population in developed countr-
ies [1]. Despite an intensive delivery of healthcare
and education to affected patients, its incidence
continues to increase, resulting in 50% or greater
mortality in a 5-year observation [1]. Loop diuret-
ics are cornerstone in the treatment of signs of
661
www .cardiologyjournal.org
CLINICAL CARDIOLOGY
Car di ology Journal
2019, Vol. 26, No. 6, 661–668
DOI: 10.5603/CJ.a2019.0114
Copyright © 2019 Via Medica
ISSN 1897–5593
ORIGINAL ARTICLE

uid overload and congestion in patients with HF.
Despite rapid relief of symptoms in patients with
acute decompensated HF, long-term use of these
agents has been consistently associated with ad-
verse events, including electrolyte disturbance,
activation of the renin–angiotensin–aldosterone
and the sympathetic nervous systems (RAAS and
SNS), which could accelerate HF progression [2, 3].
Torasemide and furosemide are representa-
tives of loop diuretics with an identical diuretic
mechanism, but different pharmacokinetic prop-
erties and additional effects. Compared to furo-
semide, torasemide has greater bioavailability,
a higher degree of protein binding, and a longer
half-life. These properties make that torasemide
works faster, longer and less frequently causes
rapid micturition than furosemide. Torasemide
after oral administration is well absorbed from the
gastrointestinal tract, even in overhydration caused
by heart, kidney and liver diseases. Moreover,
torasemide potency is 4 times greater than furose-
mide. Torasemide also has anti-aldosterone activity
and inhibits myocardial brosis and remodeling
[4–8]. According to previous studies, torasemide
decreases rates of HF hospitalizations and hospital
stay, improves exercise tolerance, quality of life,
left ventricular function, cardiac sympathetic nerve
activity, myocardial brosis, pulmonary congestion,
peripheral edema, and blood pressure compared
with furosemide [9–12]. These favorable effects of
torasemide suggest that this agent would be more
benecial than furosemide in patients with HF.
The main purpose of the present study was
comparison of the furosemide with torasemide’s
effects on HF symptoms, including New York
Heart Association (NYHA) class, uid retention
and exercise tolerance in patients with HF.
Methods
Study design
This pilot study consisted of data from the
ongoing multicenter, randomized, open, phase IV
TORNADO (TORasemide oN hemodynAmic and
Neurohormonal Stress, and carDiac remOdeling in
Heart Failure) study, registered in ClinicalTrials.
gov: NCT01942109. The study was approved by
a local ethical review board and an informed con-
sent was obtained from each patient. The detailed
methods and description of the study design have
been described previously [13]. Briey, the study
included patients who were hospitalized in years
2015–2018 in two cardiology centers in Poland,
including academic center and a district hospital.
All patients were diagnosed with HF in NYHA
II–IV class, irrespective of left ventricular ejec-
tion fraction (LVEF) and treated with optimal HF
therapy. The diagnosis of HF, according to current
guidelines [1], was based on clinical (typical HF
signs and symptoms), echocardiographic and bio-
chemical (increased concentrations of N-terminal
pro-B-type natriuretic peptide [NT-proBNP] or
BNP parameters). All demographic, clinical, etiol-
ogy of HF, laboratory data, as well as information
on medication, were collected.
Heart failure patients on a stable dose of
furosemide were randomized to the treatment
with torasemide or unchanged treatment with
furosemide (randomization 1:1). After randomiza-
tion, furosemide has been continued in its current
xed-dose or was replaced by equipotential dose of
torasemide (4:1, according to the previous studies
and manufacturer’s data [6]). Figure 1 shows the
ow chart of the study design.
Study endpoints
During the baseline hospitalization and on
control visit (3 months after enrollment) echocar-
diographic examination and 6-minute walk test
(6MWT) were performed. To assess the level of
uid retention, measurement of thoracic base im-
pedance was made using ZOE Fluid Status Monitor.
The device works in line with principle: the less
resistance — impedance measured in ohms — the
more uid is in the chest.
In the current analysis the primary endpoint
was a composite of improvement of NYHA func-
tional class, improvement of at least 50 m during
6MWT, and decrease of at least 0.5 W in fluid
retention after 3 months from recruitment. Differ-
ent composite endpoint compared to the initially
registered endpoints (i.e. events associated with
HF — deaths, hospitalization) was purposely cho-
sen because of low patient number and one-time
functional assessment at 3-month follow up.
Statistical analysis
Continuous and ordinal variables are expressed
as a median (interquartile range). Categorical data
were presented as a number of patients and per-
centages. Group comparisons were performed
using the Fisher exact test for qualitative vari-
ables and t test for quantitative, normally distrib-
uted variables, and the Mann-Whitney U test for
quantitative, non-normally distributed variables
(normality of distribution was checked with the
Shapiro-Wilk test). For all analyses, a p value of less
than 0.05 was considered statistically signicant.
662 www .cardiologyjournal.org
Cardiology Journal 2019, Vol. 26, No. 6

Results
Baseline characteristics
The current analysis of the TORNADO study
included 40 patients. During hospitalization, 60% of
them (n = 24) were randomized to further treatment
with furosemide and 40% (n = 16) to treatment
with torasemide. Median age of the study group was
66 years and 77.5% were male. Mean diuretic dose
(converted in a ratio of 4:1 on furosemide dose) was
100 mg and 70 mg in the furosemide and torasem-
ide groups, respectively (p = 0.16). Most common
etiology of HF was ischemic heart disease (50%).
Patients in the torasemide and furosemide groups
were similar in terms of age, gender, chronic dis-
eases, NYHA class, LVEF, heart rate, systolic blood
pressure, laboratory ndings (serum concentrations
of hemoglobin, creatinine, sodium, potassium, NT-
-proBNP), HF recommended pharmacotherapy (an-
giotensin converting enzyme inhibitor, angiotensin
receptor blocker, beta-blocker, mineralocorticoid re-
ceptor blocker) and implantable devices (pacemaker,
cardiac resynchronization therapy, cardioverter
debrillator). Baseline characteristics of both study
groups are presented in Table 1.
Follow-up admission
Patients completed 3-months follow-up. Dur-
ing the follow-up 7 patients were hospitalized for
HF worsening (3 vs. 4 in torasemide and furosem-
ide groups, respectively). The primary endpoint
reached 15 (94%) patients of the torasemide group
and 14 (58%) patients of the furosemide group
(p = 0.03). The changes in NYHA functional class,
6MWT and ZOE Fluid Status Monitor test from
baseline to the end of follow-up are presented
in the Table 2 and Figures 2–4. During follow-up
period, an equal percentage of patients treated
with furosemide and torasemide reached primary
endpoint in the NYHA class improvement form.
Torasemide-treated patients were more often,
but not statistically signicant, observed to reach
primary endpoint as improvement of at least 50 m
during 6MWT (n = 0.09) or decrease of at least
0.5 W in uid retention during 3 months as com-
pared to patients on furosemide (n = 0.51). These
results reect a signicant decrease in uid re-
tention and improvement in 6MWT in the whole
torasemide group as compared to whole furosemide
group in which increase in uid retention and de-
terioration in 6MWT was observed.
Figure 1. Flow chart of patient enrollment in the study; CHF — congestive heart failure; NYHA — New York Heart
Association; 6MWT — six-minute walking test.
lnclusion criteria:
signed informed consent form—
age 18 years—≥
patients with CHF—
NYHA functional class IV— II–
patients who require diuretic therapy—
stable c inical conditions during therapy— l
stable cl n cal condit on during index hospitalization— i i i Exclusion criteria:
— acute coronary syndrome
— hypertrophic cardiomyopathy
— uncontrolled hypertension
— uncontrolled diabetes
— serum potassium > 6.0 mmol/L
— serum creatinine > 2.5 mg/dL
RANDOMIZATION
RECRUITMENTALLOCATIONVISITSANALYSES
FUROSEMIDE
(n = 24)
TORASEMIDE
(n = 16)
3 months: Control visit: Assesment of endpoints
lmprovement of NYHA functional class
Improvement of at least 50 m during 6MWT
Decrease of at least 0.5 W in uid retention
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Paweł Balsam et al., Comparison of torasemide vs. furosemide in HF: Randomized TORNADO trial

Table 1. Comparison of 40 patients with heart failure treated with furosemide or torasemide.
Parameter All patients
(n = 40)
Furosemide
(n = 24)
Torasemide
(n = 16)
P
Demographics
Age [years] 66 [51–81] 65 [58–80] 74 [49–85] 0.29
Gender [male] 31 (77.5) 20 (83.3) 11 (68.8) 0.28
Body mass index [kg/m2] 30 [23–39] 30 [24–39] 30 [20–38] 0.51
Heart failure
Symptoms of HF at admission 12 (30.0) 6 (25.0) 6 (37.5) 0.40
Previous HF hospitalization 25 (62.5) 16 (67.7) 9 (56.3) 0.51
Heart failure etiology:
Ischemic 20 (50.0) 12 (50.0) 8 (50.0) 1.00
Hypertensive 5 (12.5) 2 (8.3) 3 (18.8) 0.33
Dilated cardiomyopathy 7 (17.5) 5 (20.8) 2 (12.5) 0.50
Valve disease 2 (5.0) 2 (8.3) 0 (0.0) 0.24
NYHA [class] 2 [2–3] 2 [2–3] 2 [2–3] 0.94
Ejection fraction [%] 37 [27–52] 35 [29–47] 38 [24–54] 0.93
Medical history
Smoking 20 (50.0) 13 (54.2) 7 (43.8) 0.52
Ischemic heart disease 19 (47.5) 11 (45.8) 8 (50.0) 0.80
Previous CABG/PCI 17 (42.5) 12 (50.0) 5 (31.3) 0.24
Hypertension 23 (57.5) 14 (58.3) 9 (50.0) 0.896
Diabetes 18 (45.0) 12 (50.0) 6 (37.5) 0.44
Dyslipidemia 18 (45.0) 12 (50.0) 6 (37.5) 0.44
Atrial fibrillation 17 (42.5) 9 (37.5) 8 (50.0) 0.58
Cardiac electronic implantable device 17 (42.5) 9 (37.5) 8 (50.0) 0.58
Stroke/TIA 2 (5.0) 2 (8.3) 0 (0.0) 0.27
Peripheral vascular disease 5 (12.5) 3 (12.5) 2 (12.5) 1.00
Chronic kidney disease 14 (35.0) 9 (37.5) 5 (31.3) 0.08
Clinical status
Heart rate [bpm] 75 [60–100] 75 (18.5) 80 [60–100] 0.95
Systolic BP [mmHg] 135 [110–160] 135 [116–160] 133 [100–150] 0.29
Diastolic BP [mmHg] 78 [64–101] 80 [70–101] 70 [60–80] 0.07
Laboratory findings
NT-proBNP [pg/mL] 1681
[483–5902]
2106
[656–7032]
1273
[374–5435]
0.30
Sodium concentration [mmol/L] 141 [137–146] 141 [137–146] 141 [138–144] 0.56
Potassium concentration [mmol/L] 4.4 [3.9–4.9] 4.5 [3.9–4.9] 4.4 [3.9–4.9] 0.86
Creatinine concentration [mg/dL] 1.3 [0.9–1.8] 1.3 [1.0–1.9] 1.2 [0.7–1.6] 0.10
Pharmacotherapy
Beta-blocker 34 (89%)
N = 38
22 (96%)
N = 23
14 (93%)
N = 15
0.76
ACEI 26 (68)
N = 38
17 (74)
N = 23
9 (60)
N = 15
0.37
Angiotensin receptor blocker 7 (18)
N = 38
2 (8.7)
N = 23
5 (33)
N = 15
0.06
Aldosterone antagonist 23 (61)
N = 38
15 (65)
N = 23
9 (60)
N = 15
0.75
Values are showed as median (interquartile range) or number (percentage); ACEI — angiotensin-converting enzyme inhibitor; BP — blood
pressure; CABG — coronary artery bypass grafting; HF — heart failure; PCI — percutaneous coronary intervention; TIA — transient ischemic
attack
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Cardiology Journal 2019, Vol. 26, No. 6

Discussion
The results of this study showed that patients
randomized to torasemide had a higher likelihood
of reaching the primary composite endpoint of
improvement of NYHA functional class, decreased
uid retention, elongated walking distance com-
pared to patients randomized to furosemide. This
may indicate that diuretic effect of torsemide com-
pared to furosemide can cause the higher loss of
body water leading to greater weight loss that can
facilitate walking. Signicant, but not statistically,
improvement in walking distance and decreased
uid retention among torasemide-treated patients
may be also explained by phenomenon of “regres-
sion to the mean” — which describes the tendency
of extreme measurement on a rst occasion to
become less extreme when checked again. In this
study, it was easier for a patient on torasemide to
have a larger improvement in 6MWT and decrease
Figure 3. Changes in six-minute walk test (6MWT) from
baseline to the end of follow-up. The proportion of
patients with/without improvement in walking distance
(≥ 50 m) during 6MWT from baseline to the end
of 3-month follow-up in torasemide-treated patients
(p= 0.09 compared to furosemide-treated patients).
Figure 2. Changes in New York Heart Association
(NYHA) functional class from baseline to the end of fol-
low-up. The proportion of patients with/without NYHA
class improvement (≥ 1 NYHA class) from baseline
to the end of 3-month follow-up in torasemide-treated
patients (p = 0.77 compared to furosemide-treated
patients).
Figure 4. Changes in fluid retention from baseline to the
end of follow-up. The proportion of patients with/with-
out decrease (≥ 0.5 W) in fluid retention from baseline
to the end of 3-month follow-up in torasemide-treated
patients (p = 0.51 compared to furosemide-treated
patients).
0
20
10
30
40
50
60
70
80
Patients with equal or
worsened NYHA class
Patients with
improvement
of ≥ NYHA class
75%
% total patients per group
75%
25% 25%
Torasemide
Furosemide
0
20
10
30
40
50
60
70
80
Patients with equal or
worsened distance
during 6MWT
Patients with improvement
of at least 50 m
during 6MWT
37%
% total patients per group
75%
63%
25%
Torasemide
Furosemide
0
20
10
30
40
50
60
70
Patients with equal or
worsened uid
retention
Patients with decrease
at least 0.5 W
in uid retention
% total patients per group
58%
37%
63%
42%
Torasemide
Furosemide
Table 2. Changes in the components of the primary from baseline to the end of 3-month follow-up.
Variable Furosemide Torasemide
On
admission
3-month
follow up
P On
admission
3-month
follow up
P
ZOE® Fluid Status Monitor [Ohm] 17 (15–24) 18 (15–23) 0.68 18 (15–24) 17 (15–19) 0.05
NYHA class 3 (2–3) 2 (1–3) 0.37 3 (2–4) 2 (2–3) 0.18
6MWT [m] 309 (172–450) 320 (120–454) 0.10 243 (120–432) 340 (100–500) 0.29
Values are showed as median (interquartile range); NYHA — New York Heart Association; 6MWT — six-minute walk test
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Paweł Balsam et al., Comparison of torasemide vs. furosemide in HF: Randomized TORNADO trial

in uid retention if the initial walking distance was
too low and uid retention was too high.
Recently published data from the QUALIFY
(QUAlity of adherence to guideline recommen-
dations for Life-saving treatment in HF) survey,
reported 70% adherence to the guideline-recom-
mended drugs what reects fairly satisfactory HF
therapy [14]. The current HF guidelines recom-
mended the use of loop diuretics as a class I indi-
cation to improve symptoms in HF patients with
both reduced and preserved LVEF [1]. There is no
clear answer which of the loop diuretics should be
preferred. The favourable use of furosemide in HF
might be explained by its early market introduction
in 1960s, whereas torasemide was approved by
Food and Drug Administration in 1990s and became
generic at the beginning of the twenty-rst century.
However, some studies suggest that torasemide
outperform furosemide’s clinical and economic
properties by reducing hospital admissions and
in-hospital stay [15–17].
Furosemide, the most commonly used loop
diuretic in clinical practice, is known to activate the
RAAS and the SNS, which could accelerate HF pro-
gression. In contrast to furosemide, torasemide was
shown to have favorable effect on RAAS inhibition,
through blockade of the aldosterone receptor [4, 5].
Our analysis revealed that torasemide-treated pa-
tients tended to gain more benets in symptomatic
HF therapy than furosemide what emphasized the
importance of obtaining prospective data comparing
these two loop diuretics.
There are no previous studies showing direct
comparison of torasemide and furosemide on uid
retention. Our study showed more pronounced
decrease in uid retention with torasemide than
furosemide treatment. This probably translated
into improved NYHA class and elongated walking
distance in the torasemide group. Recent analysis
from the Heart Failure Registries of the European
Society of Cardiology revealed that use of torasem-
ide was associated with signicantly lower NYHA
class comparing to furosemide treatment (p =
= 0.04). During follow-up torasemide use was associ-
ated with a lower risk (12.9% vs. 20.0%; p = 0.03)
of worsening ≥ 1 NYHA functional class (12.9% vs.
20.0%; p = 0.03) [18]. TORIC (TORasemide In
Congestive HF) study that revealed signicantly
higher efciency of torasemide than furosemide
and other diuretics in functional improving of at
least 1 grade in NYHA class (45.8% vs. 37.2%;
p = 0.00017) [19]. It is in line with the metanalysis
of Kido et al. [20] that showed that torasemide is
associated with statistically signicant improve-
ment in NYHA functional class for patients with HF
compared with furosemide (p = 0.0004). However,
torasemide did not provide signicant benets in
reducing mortality or rehospitalization rates for
HF (p = 0.15) or cardiovascular disease (p = 0.22)
compared with furosemide. Moreover, there was
no signicant difference in mortality between tor-
semide and furosemide (p = 0.99).
According to large international ASCEND-
HF trial, clinicians tend to use torasemide in the
setting of patients with features of more severe
disease including refractory volume overload [21].
The preferential use of torsemide in these circum-
stances may be related to torasemide’s smaller
inter- and intraindividual variation in bioavailabil-
ity, longer action increased bioavailability, longer
half-life and maintained absorption in the setting
of intestinal edema [6, 21, 22]. Moreover, diuretic
therapy with torasemide instead of furosemide
optimizes the quality of daily life of patients with
HF by reducing number of mictions at 3, 6 and 12 h
after diuretic intake, and urgency to urinate
[6, 13, 22]. Other studies have also demonstrated im-
provement in sympathetic nerve activity as well as
decreased left ventricle volumes and levels of BNP
with torsemide compared to furosemide therapy
[23, 24]. Additional benets with torsemide over
furosemide include less urinary potassium loss re-
sulted in reduced arrhythmia burden [25]. In DiNi-
colantonio et al. [7] meta-analysis of randomized
controlled trials in 471 patients with systolic HF,
compared with furosemide, torasemide caused
a 14% reduction in all-cause mortality. It is in line
with the TOrasemide In Congestive Heart Failure
(TORIC) study results that reported signicantly
lower mortality in the torasemide (n = 17, 2.2%)
than in furosemide/other diuretics groups (n = 27,
4.5%; p < 0.05) [19]. Analysis of the Polish parts of
Heart Failure Registries of the European Society
of Cardiology, Pilot and Long-Term, revealed that
use of torasemide was associated with a signicant
24% risk reduction of the composite endpoint of all-
cause death and hospitalization for worsening HF
(26.4% vs. 34.7%; p = 0.04). These benets may
be due to the additional advantages of torasemide
such as anti-aldosterone effect [18].
Patients discharged after hospitalization for
HF remain at high risk of death and hospital read-
mission due to recurrence of the symptoms of HF.
Therefore, every effort should be made to develop
an optimal treatment strategy in this group of pa-
tients. It is worth mentioning a recently-started
ToRsemide compArisioN With furoSemide FOR-
Management of Heart Failure (TRANSFORM-HF)
666 www .cardiologyjournal.org
Cardiology Journal 2019, Vol. 26, No. 6

study that aim is to compare the effects of furosem-
ide versus torsemide on clinical outcomes over
12 months in approximately 6000 patients previously
hospitalized for HF [26].
Limitations of the study
The main limitation of the study is the small
sample size of the assessed population. The small
number of participants did not enable assessment
of the impact of torasemide and furosemide in
different clinically relevant subgroups i.e. elderly,
patients with chronic kidney disease, dilated car-
diomyopathy. Noteworthy, the number of patients
was sufcient to observe differences between the
effects of torasemide and furosemide on clinical
outcomes in HF patients. Moreover, the size of
studied population made it possible to follow all
subjects closely for the duration of the study and
gathering considerably detailed information on
each study participant.
Conclusions
Based on our study, patients randomized to
torasemide had a higher likelihood of improve-
ment of NYHA functional class, decreased fluid
retention, elongated walking distance during
6MWT compared to patients randomized to furo-
semide entire follow-up period. This may indi-
cate that diuretic effect of torsemide compared
to furosemide can cause the higher loss of body
water leading to greater weight loss that can
facilitate walking. The above results and the
impact of both drugs on the designed endpoint
will confirm final results of TORNADO trial with
the intention of being published by the end of
2020. However, further large-scale randomized
trials comparing loop diuretic strategies would
provide an opportunity to improve HF outcomes
and reduce health care expenditures with cur-
rently available therapies.
Conict of interest: None declared
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Cardiology Journal 2019, Vol. 26, No. 6