Should Torsemide Be the Loop Diuretic of Choice in Systolic Heart Failure?

James J DiNicolantonio

Future Cardiol. 2012;8(5):707-728.

Conclusion

In this comprehensive systematic review of randomized controlled trials, which included a total number of 471 patients, torsemide significantly reduced HF and CV-related hospital readmissions compared with furosemide. However, the results have some limitations. Of particular note, trials were randomized but not double-blind. Both trials were multicentered and included a few hundred patients. This systematic review evaluated 471 patients, encompassing 89, 137 and 57 HF and CV readmissions and deaths, respectively (Figure 5).

In 2006, the annual US healthcare cost for treating patients with HF was US$29.6 billion.^[49] At least 70% of this cost was due to HF readmissions, with an estimated cost of $20.72 billion.^[50] Taking into account the results of this meta-analysis (RR: 59% reduction in HF readmissions), switching patients on furosemide to torsemide could save the US healthcare system approximately $12.22 billion/year in HF readmissions alone.^[49–51] This does not include the money that would be saved from a reduction in CV readmissions, which would be expected to be substantial.

HF results in a decrease in cardiac output with subsequent activation of the renin–angiotensin–aldosterone system in order to maintain target-organ blood flow.^[52] Furthermore, arginine vasopressin (antidiuretic hormone) is released by the posterior pituitary gland causing free water retention by the kidneys.^[53] Thus, many HF patients are placed on loop diuretics to prevent pulmonary and peripheral edema, which helps to keep them out of the hospital.

Furosemide is the most commonly used loop diuretic for systolic HF patients. However, torsemide has distinct features giving additional benefits beyond a natriuretic and diuretic effect.^[18–22] These pleiotropic effects seem to give torsemide an advantage compared with furosemide, such as a significant reduction in HF and CV hospitalizations compared with furosemide.^[36,48] More importantly, the TORIC trial showed that torsemide is more efficacious at improving NYHA functional class and is associated with a greater than 50% reduction in mortality compared with furosemide and other diuretics.^[53] The results of this systematic review and the TORIC trial should encourage a large multicentered clinical trial to confirm that torsemide improves morbidity and mortality in patients with systolic HF.

HF consensus guidelines do not distinguish one loop diuretic from another.^[54,55] However, it is clear that torsemide is a different loop diuretic compared with furosemide with greater evidence to support its use.^[36,48,53] Compared with furosemide, the 10.5-month number needed to prevent one HF or CV readmission with torsemide was six and nine, respectively (Table 5).

Loop diuretics such as torsemide and furosemide are used for the symptomatic treatment of CHF,^[53] and are currently recommended for the treatment of chronic HF.^[53–55] Compared with furosemide, torsemide has a longer half-life, longer duration of action and a higher and less variable bioavailability.^[1] This article demonstrates that compared with furosemide, torsemide improves hard outcomes as well as cardiac function and humoral factors. Thus, torsemide should be the loop diuretic of choice in patients with HF compared with furosemide.

In direct randomized comparison trials, torsemide improves fatigue, hospitalizations for HF and CV causes, decreases hospital stay, improves exercise tolerance, quality of life, urinations, urinary urgency, left ventricular function, humoral factors, cardiac sympathetic nerve activity, myocardial fibrosis, left ventricular remodeling, hypokalemia, diuresis, natriuresis, pulmonary congestion, edema, blood pressure and weight compared with furosemide, yet furosemide is the most prescribed loop diuretic. Taking into account the previously mentioned benefits, torsemide not furosemide should be the loop diuretic of choice in patients with HF.

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Table 1. Properties of loop diuretics.
Diuretic	Oral bioavailability	Initial dose (mg)	Maintenance dose (mg)	Max dose (mg)	iv. to p.o. conversion	Elimination	Duration of action (h)
Torsemide	80–100%	5–10 q.d.	10–20	200	1:1	80% liver 20% renal^†	18–24
Furosemide	10–90%	20–40 q.d.–b.i.d.	40–240	600	1:2	50% renal (unchanged)^‡ 50% renal (conjugation)^‡	4–6
Bumetanide	80–100%	0.5–1 q.d.–b.i.d.	1–5	10	1:1	50% liver^†	6–8

†More torsemide and bumetanide reaches the tubular fluid in patients with liver disease due to a prolonged half-life.
‡Furosemide accumulates in renal insufficiency due to a decrease in both urinary excretion and renal conjugation.
b.i.d.: Twice daily; iv.: Intravenous; p.o.: Per orum; q.d.: Once daily.
Data taken from [59–61].

Table 2. Clinical trials on surrogate markers in systolic heart failure: torsemide versus furosemide.
Study (year)	n	Results	Comments	Ref.
Broekhuysen et al. (1986)	18	Daily urinary volume increased more with torsemide compared with furosemide (p < 0.015). Decline in diuresis was significantly slower after torsemide vs furosemide (p < 0.05). Torsemide caused a larger decrease in diastolic blood pressure compared with furosemide in the morning (p < 0.001) and in the evening (p < 0.02)	During torsemide treatment, diuresis never dropped below baseline values throughout the 24 h interval, whereas diuresis dropped below baseline during the 4–12 h interval in patients assigned to furosemide 40 mg. On a weight basis, torsemide was eight-times more natriuretic and chloruretic than furosemide, but was only three-times more kaliuretic	[27]
Scheen et al. (1986)	13	When compared with placebo and furosemide 40 mg, only torsemide 20 mg induced a significant increase in urine volume (68% larger [2p < 0.001]), natriuresis (+137% [no p-value given]), urinary chloride excretion (+246% [2p < 0.02]) and caused a significant decrease in free water clearance over the 24 h interval (-0.65 ml/min, 2p < 0.02 vs placebo, -0.51 ml/min, 2p < 0.05 vs furosemide 40 mg), respectively	A rebound effect of increased sodium and water retention (a decrease in diuresis compared with placebo) was observed 12 h after the administration of furosemide 40 mg, which was not observed with torsemide even after 24 h after administration. In patients with chronic HF, torsemide 20 mg was significantly more effective compared with furosemide 40 mg at increasing diuresis, natriuresis, chloruresis and free water clearance	[40]
Archhammer et al. (1988)	111	Within the 4 groups that were switched from furosemide to torsemide body weight significantly decreased (p < 0.05). Twenty eight patients had residual edema at the beginning of the study on furosemide vs only five patients at the end of the study, after treatment with torsemide. Thus, 23 patients on furosemide with edema became free of edema after torsemide treatment	There was no significant difference in body weight either before or after treatment between the groups that received either 5 or 10 mg torsemide during the entire study. The 83 patients without edema before starting torsemide remained free of edema throughout the trial	[41]
Herchuelz et al. (1988)	18	Daily and fractional Na⁺ and CL⁻ clearances were increased significantly more with torsemide compared with furosemide (p < 0.0025 or less). Torsemide decreased blood pressure significantly more than furosemide in the morning (p < 0.001) and in the evening (p < 0.02)	On a weight basis, torsemide 10 and 20 mg were 6.9- and 9.5-times more natriuretic (mean: 8.2), respectively, than furosemide and 8.2- and 7.3-times more chloruretic (mean: 7.8), respectively, than furosemide (p < 0.00001, in favor of torsemide)	[28]
Fiehring et al. (1990)	15	Torsemide was the only group to demonstrate a significant decrease in SPAP at 100 watts. The RPP was continuously lower after torsemide at the different watt-steps, whereas it was even higher after furosemide for the 50-, 75- and 100-watt tests, mainly due to a higher heart rate with furosemide	As cardiac demand increases, furosemide becomes less effective at reducing SPAP and DPAP, whereas torsemide becomes more effective. It seems that torsemide lowers energy demand of the heart, whereas furosemide raises energy demand of the heart during increasing levels of exercise	[42]
Stauch et al. (1990)	114 enrolled (104 evaluated)	After 4 weeks of treatment with torsemide 10 mg, torsemide 20 mg and furosemide 40 mg, 94, 100 and 79% improved, respectively, from NYHA class III to NYHA class I or II. Thus, almost all patients given torsemide starting with NYHA class III at baseline improved	Torsemide was more effective with respect to symptoms removed or improved. Torsemide 5 and 10 mg are more effective at improving body weight and NYHA functional class compared with furosemide 40 mg	[43]
Goebel (1993)	70	Mean weight loss in the 10 mg torsemide group was significantly greater than in the 40 mg furosemide group at week 4 (-2.20 kg vs -1.07 kg, p = 0.04). Weight loss was also significantly greater in the 20 mg torsemide group vs the 40 mg furosemide group at weeks 4 and 6 (-2.47 kg vs -1.07 kg and -2.96 kg vs -1.29 kg, p = 0.01), respectively. There was no significant improvement in edema at week 6 in the 40 mg furosemide group (p = 0.118), whereas there was a marginally significant effect for the 10 mg torsemide group (p = 0.057) and a highly significant improvement in the 20 mg torsemide group (p < 0.001). There was no significant improvement in heart size at 6 weeks with the 40 mg furosemide group (p = 0.070), whereas there was a significant improvement in heart size for the 10 mg (p = 0.008) and 20 mg torsemide groups (p = 0.001). There was significantly less edema and pulmonary congestion in the 20 mg torsemide group than in the 10 mg torsemide group (edema, p = 0.003; pulmonary congestion, p = 0.03) and the 40 mg furosemide group (edema, p = 0.001; pulmonary congestion, p = 0.02)	20 mg of torsemide q.d. was significantly more effective than 40 mg of furosemide q.d. in improving CHF symptoms, reducing body weight, reducing pulmonary congestion and reducing edema. Torsemide-treated patients were the only patients to demonstrate a significant improvement in heart size	[44]
Vargo et al. (1995)	16	Torsemide was more rapidly absorbed than furosemide (T_max = 1.1 vs 2.4 h), respectively. The bioavailability of torsemide was also greater and less variable than that of furosemide (89.3 vs 71.8%, coefficient of variation was 8.9 vs 29.8%), respectively	CHF does not affect the rate or level of absorption of torsemide after oral administration, whereas delayed absorption and lowered bioavailability occurs in CHF patients on furosemide	[1]
Ferrara et al. (1997)	40	A statistically significant decrease in diastolic blood pressure from baseline to day 7 was observed with torsemide (-9.8%, p < 0.05), day 14 (-9.1%, p < 0.05) and on day 21 (-8.1%, p < 0.05) of treatment with a similar value at the end of treatment. Furosemide did not significantly decrease diastolic blood pressure. Torsemide significantly increased EF from 35.1 to 40.2% (p < 0.001), whereas furosemide did not. Kaliuresis increased significantly with respect to baseline on days 7, 14, 21 and 28 in patients on furosemide (p < 0.05); no significant increase was found in patients on torsemide	Torsemide has potassium sparing effects and significantly lowers blood pressure and improves EF, whereas furosemide does not	[29]
Yamato et al. (2003)	50	At 6 months, in patients treated with torsemide, peak E velocity and E/A ratio were increased (p < 0.001), DcT (p < 0.001) and IRT (p < 0.005) were shortened. Furthermore, LVDd (p < 0.005) and LVMI (p < 0.005) were reduced. The BNP was lowered (p < 0.001), PARC was increased (p < 0.001) and plasma aldosterone was increased (p < 0.001). None of these parameters changed in the furosemide group	LVDd was smaller (p < 0.05), LVMI was smaller (p < 0.05), E/A was greater (p < 0.05), PARC was higher (p < 0.05), plasma aldosterone concentration was higher (p < 0.05), and plasma BNP concentration was lower (p < 0.05) in torsemide treated patients than furosemide treated patients at 6 months	[45]
Lopez et al. (2004)	39	CVF after treatment was significantly lower in the torsemide group compared with the furosemide group (p < 0.005). Furosemide did not significantly affect CVF in the overall population, patients with systolic or diastolic HF (7.29 vs 6.47%, p = NS, 6.66%, p = NS, and 6.10%, p = NS, respectively). Torsemide was associated with a significant reduction in serum PIP (143 vs 111 ug/l, p < 0.01), whereas serum PIP did not change in the furosemide group (133 vs 133 ug/l, p = NS). Serum PIP was lower after torsemide treatment compared with furosemide treatment (p < 0.01). The number of patients deomonstrating improvement of at least one grade in NYHA functional class was greater in the torsemide group compared with the furosemide group (p < 0.05). EF and left ventricular chamber stiffness had trends towards improvement with torsemide but not furosemide	Torsemide but not furosemide improves myocardial fibrosis in CHF patients and causes a significantly greater improvement in NYHA functional class	[20]
Tsutamoto et al. (2004)	60	Plasma aldosterone level in the coronary sinus was significantly lower than that in the aortic root (73.1 vs 56.9 pg/ml; p < 0.001) on furosemide, whereas there was no difference in plasma aldosterone levels between the carotid sinus and aortic root in the torsemide group (85.4 vs 83.1 pg/ml). Plasma procollagen type III aminoterminal peptide (a biochemical marker of fibrosis) in the carotid sinus was significantly lower in the torsemide group than in the furosemide group (0.52 vs 0.67 U/ml; p < 0.05)	The transcardiac gradient (aortic root to carotid sinus) of aldosterone and the extraction ratio of aldosterone in the aortic root were significantly lower in the torsemide group than those in the furosemide group. Torsemide has aldosterone receptor antagonist abilities in the heart	[18]
Naganuma et al. (2005)	32	When furosemide (average 41 mg) taken daily for at least 4 months was switched to torsemide (average 8.1 mg) daily for 3 months, the break point in double product vs work rate relationship was significantly improved from 25 watts to 29 watts; p = 0.004) and peak exercise improved from 36 to 39 watts; p = 0.003). Moreover, torsemide significantly improved left ventricular EF (from 45 to 47%; p = 0.016) and showed a trend towards a decrease in BNP (from 142 to 116 pg/ml; p = 0.08). Average heart rate over 24 h significantly decreased once switched to torsemide (from 80 to 76 beats/min; p = 0.011)	Chronic congestive heart failure (NYHA classes II and III) patients that were pretreated with ACE inhibitors (88%), β-blockers (53%), digitalis (47%). Switching chronic HF patients on furosemide to torsemide (at 1/5th the furosemide dose) provides additional beneficial effects	[46]
Kasama et al. (2006)	40	In patients receiving torsemide, TDS decreased from 44 to 36 (p < 0.001), H/M ratio increased from 1.61 to 1.77 (p < 0.001), washout rate decreased from 52 to 41% (p = 0.001), LVEDV decreased from 173 to 147 ml (p < 0.001), LVESV decreased from 117 to 95 ml (p < 0.001) and LVEF tended to increase (from 31 to 34%, NS). These parameters did not change significantly in patients receiving furosemide. NYHA functional class of patients in the torsemide group was improved significantly more than in the furosemide group (p < 0.05)	Compared with furosemide, torsemide can improve cardiac sympathetic nerve activity and attenuate left ventricular remodeling in patients with CHF	[30]
Lopez et al. (2007)	22	There were significantly more patients in the torsemide group showing an improvement of at least 1 grade in NYHA functional class compared with the furosemide group (p < 0.01). CVF significantly decreased in the torsemide group (p < 0.01) but remained unchanged in the furosemide group. The difference between the change in myocardial fibrosis from baseline between torsemide and furosemide was significantly in favor of torsemide (-43.20 vs -4.11%; p < 0.05), respectively. Torsemide caused a significant reduction in PICP, whereas there was no change with furosemide (p < 0.01). Furthermore, serum PICP at 8 months was significantly lower in the torsemide group compared with the furosemide group (p < 0.05, -19.30 vs -4.12%; p < 0.05 for the difference in change from baseline)	Torsemide has the ability to interfere with the myocardial PCP/PCPE system, which may contribute to its antifibrotic mechanism in the heart. These benefits were shown on top of ACE-inhibitors and ARBs. PCP activation significantly decreased in the torsemide group (p < 0.05), whereas there was no change in the furosemide group. Moreover, the expression of PCP zymogen and PCP active form significantly increased in the furosemide group (p < 0.05), whereas there was no change in the torsemide group	[21]
Senzaki et al. (2008)	102	HF index showed a trend for improvement in patients on torsemide (7.4–6.8; p = 0.07). BNP significantly decreased (50–45 pg/dl) on torsemide. 24-h urinary output significantly increased (298–346 ml) when furosemide was switched to torsemide (no p-value). Potassium increased from 4.2 to 4.3 mEq/l and HF symptoms showed a trend for improvement on torsemide. None of these parameters were significantly affected by furosemide	Torsemide improves signs and symptoms of HF while having a potassium-sparing effect; this was not seen with furosemide	[47]

ACE: Angiotensin-converting enzyme; ARB: Angiotensin receptor blocker; BNP: Brain natriuretic peptide; CHF: Congestive heart failure; CVF: Collagen volume fraction; DcT: Deceleration time; DPAP: Diastolic pulmonary arterial pressure; E/A: Ratio between early and late ventricular filling velocity; EF: Ejection fraction; HF: Heart failure; H/M: Heart to mediastinum ratio; IRT: Isovolemic relaxation time; LVDd: Left ventricular diastolic diameter; LVEDV: Left ventricular end-diastolic volume; LVEF: Left ventricular ejection fraction; LVESV: Left ventricular end-systolic volume; LVMI: Left ventricular mass index; NS: Nonsignificant; NYHA: New York Heart Association; PARC: Plasma active renin concentration; PCP: Procollagen C-proteinase; PCPE: Procollagen type I carboxy-terminal proteinase enhancer; PICP: Procollagen I C-terminal propeptide; PIP: Carboxy-terminal peptide; q.d.: Once daily; RPP: Rate pressure product; SPAP: Systolic pulmonary arterial pressure; TDS: Total defect score; Tmax: Time to maximum concentration.

Table 3. Murray and Muller *et al.* trials.
End point	Torsemide versus furosemide
HF readmissions	60% reduction (p < 0.01)
Cardiovascular readmissions	34% reduction (p < 0.02)
All-cause mortality	23% reduction (p = 0.54)
Hospital stay	64% reduction (106 vs 294 days, p = 0.02)
Tolerability	p = 0.0001
Improvement in daily restrictions	p = 0.0002
The number of urinations at 3, 6 and 12 h after diuretic intake	p < 0.001, improvement at all times points with torsemide vs furosemide
Improvement in NYHA functional class	p < 0.014, only significant with torsemide
Fatigue scores at 2, 8 and 12 months	p < 0.05

HF: Heart failure; NYHA: New York Heart Association.
Data taken from [36,48].

Table 4. Clinical trials on hard end points: torsemide versus furosemide.
Study	n	Results	Comments	Ref.
Murray et al. (2001)	234	Compared to furosemide, torsemide caused less readmissions for HF (19 [17%] vs 39 [32%], p = 0.01), CV causes (50 [44%] vs 71 [59%], p = 0.03) in 'patients with at least 1 readmission' and less readmission for HF (23 vs 61, p < 0.01) and for all CV causes (78 vs 130, p = 0.02) when total readmissions were analyzed. Furthermore, patients on torsemide had significantly fewer hospital days for HF (106 vs 296 days, p = 0.02) and a trend for less hospital days due to CV causes (364 vs 614, p = 0.06)	After 12 months of follow-up. ACE-inhibitor use at baseline was 81% and 77% for the torsemide and furosemide groups, respectively. Average daily dose of 136 mg of furosemide and 72 mg of torsemide.Torsemide also significantly improved fatigue scores at months 2, 8 and 12 compared with furosemide	[48]
Muller et al. (2003)	237	Two and three HF hospitalizations in the torsemide and furosemide groups (RR: 0.63 [95% CI: 0.11–3.69]), respectively. Eight hospitalizations due to CV causes in both groups (RR: 0.94 [95% CI: 0.37–2.43]. Eight and six deaths in the torsemide and furosemide groups (RR: 1.26 [95% CI: 0.45–3.51]), respectively	After 9 months of follow-up. Mean doses for torsemide and furosemide were 11.36 and 40.04 mg, respectively. All patients (100%) were on ACE-inhibitors. A total of 194 patients completed the trial	[36]

ACE: Angiotensin-converting enzyme; CV: Cardiovascular; HF: Heart failure; RR: Relative risk.

Table 5. Torsemide versus furosemide in systolic heart failure.
Outcome	Trials	n	Results, RR (95% CI)	p-value	NNT (10.5 months)
HF readmissions	Two active-controlled	471	0.41 (0.28, 0.61)	<0.0001	6^†
Cardiovascular readmissions	Two active-controlled	471	0.77 (0.60, 0.98)	0.03	9^‡ 11^§

†Data from total HF readmissions.
‡Data from total cardiovascular readmissions.
Data from patients with at least one cardiovascular readmission, p-value for patients with at least one cardiovascular readmission.
HF: Heart failure; NNT: Number needed to treat; RR: Relative risk.

Box 1. Advantages of torsemide versus furosemide.
*Pharmacological properties* Longer duration of action Quicker onset of action Greater and less variable bioavailability Food decreases fuorsemide's but not torsemide's diuretic activity (bioavailability, T _max and C _max) Potassium-sparing effect Magnesium-sparing effect Less postdiuretic 'rebound effect' of sodium and water retention Less chance of ototoxicity: furosemide but not torsemide is metabolized by the kidneys and thus in renal dysfunction furosemide will accumulate, increasing the risk of ototoxicity Inhibition of the RAAS system: inhibition of angiotensin-II and aldosterone Greater binding to luminal tubular receptors Bioavailability is not affected by CHF or renal dysfunction On a milligram-to-milligram basis, the natriuretic and chloruretic effects of torsemide are approximately eight-times that of furosemide Torsemide is 97–99% protein bound whereas furosemide is 95% protein bound. A loop diuretic with greater than 95% protein binding limits its glomerular filtration. This allows the diuretic to stay trapped in the vascular space (bound to serum proteins) so that it can be consistently delivered to secretory sites of proximal tubule cells (i.e., more torsemide is delivered to the site of action versus furosemide due to higher protein binding) Hypoalbuminemic states (celiac disease, Crohn's disease, short bowel syndrome, liver dysfunction such as hepatitis, cirrhosis or hepatic carcinoma or nephrotic syndrome). A decrease in systemic albumin decreases the amount of medication bound to albumin in the blood, allowing more of the loop diuretic to be trapped in the interstitial space. This leads to less drug reaching the site of action in the tubular lumen. Furthermore, hypoalbuminemia increases renal glucuronidation and this increases furosemides metabolism (this will not occur with torsemide)
*Clinical effects* Greater effects on blood pressure Greater reduction in HF- and CV-related hospital readmissions Decreased length of hospital stay Better quality of life: less nocturia, micturition and urinary urgency Greater improvement in NYHA functional class (fatigue, heart size, leg edema, pulmonary congestion and ejection fraction are all improved significantly more with torsemide) Inhibits the sympathetic nervous system (norepinephrine): shows improvement in myocardial 123-iodine metaiodobenzylguanidine uptake and improves total defect score, washout rate and heart to mediastinum ratio Decreases cardiac fibrosis: offers the potential advantage of decreased sudden death from arrhythmias (due to cardiac fibrosis), improvement in cardiac function and improvements in NYHA functional class especially in patients with diastolic dysfunction (who are more affected by cardiac fibrosis) Increased compliance: once daily vs twice daily dosing Reduces thiazide diuretic induced potassium and magnesium loss Increased diuresis and natriuresis Increased glomerular filtration rate

CHF: Congestive heart failure; CV: Cardiovascular; HF: Heart failure; NYHA: New York Heart Association: RAAS: Renin–angiotensin–aldosterone system.

Sidebar

Executive Summary

A systematic review of randomized trials using OVID MEDLINE, Excerpta Medica, Web of Science, PubMed and Google Scholar was performed. Two randomized trials comparing furosemide with torsemide in 471 patients with systolic heart failure (HF) were identified. Compared with furosemide, torsemide significantly reduced HF readmissions (relative risk: 0.53, 95% CI: 0.33–0.84) and cardiovascular readmissions (relative risk: 0.77, 95% CI: 0.60–0.98) in patients with "at least 1 readmission".
In direct comparison trials, torsemide significantly improves fatigue, reduces HF and cardiovascular-related hospital readmissions, reduces hospital stay, improves exercise tolerance, quality of life, urinations, urinary urgency, left ventricular function, humoral factors, cardiac sympathetic nerve activity, myocardial fibrosis, left ventricular remodeling, hypokalemia, diuresis, natriuresis, pulmonary congestion, edema, blood pressure and weight compared with furosemide.
On a milligram-to-milligram basis, the natriuretic and chloruretic effects of torsemide are approximately eight-times that of furosemide.
Compared to furosemide, torsemide has a longer half-life, longer duration of action, and a higher and less variable bioavailability.
Compared to furosemide, torsemide significantly reduced total heart failure readmissions (relative risk: 0.41, 95% CI: 0.28–0.61; p < 0.0001), I ² = 0%.
Compared to healthy individuals, the rate of absorption of torsemide and the subsequent diuretic effect, are not affected by congestive HF (CHF), whereas the absorption rate and diuretic effect of furosemide and bumetanide are reduced in CHF. Thus, torsemide retains its pharmacodynamic properties in patients with CHF regardless of the HF severity, whereas furosemide's pharmacodynamics (diuretic and natriuretic effects) are significantly diminished.
Furosemide is metabolized in the kidneys leading to accumulation of furosemide but not torsemide in renal dysfunction. The resulting increased accumulation of furosemide in patients with lowered kidney function results in an increased risk of ototoxicity with furosemide compared with torsemide.
Torsemide has antialdosterone, antifibrotic and vasodilatory properties. These properties are not shared by furosemide.
Torsemide should be the loop diuretic of choice compared with furosemide in patients with systolic HF.