Torsemide over furosemide as first-line loop diuretic for HF

When starting a new loop diuretic for a patient with heart failure, strongly consider torsemide over furosemide, Anthony C. Breu, MD, advised at SHM Converge, the annual conference of the Society of Hospital Medicine.

“Whether or not you take a patient who’s already on furosemide and you make the switch to torsemide is a little bit tougher for me to advocate, though that has happened in clinical trials,” said Dr. Breu, assistant professor of medicine at Harvard Medical School, Boston, who spoke May 5 at the Converge session “Things We Do for No Reason.” He co-presented the session with Leonard Feldman, MD, SFHM, director of the Osler Medical Residency Urban Health Track and associate professor at Johns Hopkins Medicine, Baltimore.

“If you consider doing this it would make sense to do so concert with the outpatient primary doctor and the outpatient cardiologist,” Dr. Breu said. “But in my review of the literature, it’s at least worth having these discussions, particularly for a patient who has multiple readmissions for heart failure. That may be a time to pause and ask: ‘Could torsemide be of benefit here?’ ”

In Dr. Breu’s opinion, there are at least three reasons why consider torsemide should be considered a first-line treatment for heart failure. For one thing, the current evidence says so. In a trial published in 2001, researchers randomized 234 patients with heart failure to receive torsemide or furosemide for 1 year. The percentage of patients who had one or more hospital readmissions was lower among those who received torsemide, compared with those who received furosemide in the torsemide group for heart failure (17% vs. 32%, respectively; P < .01) and for other cardiovascular causes (44% vs. 59%; P = .03). In addition, the number of total admissions was numerically lower for patients in the torsemide group, compared with the furosemide group for heart failure (23 vs. 61; P < .01) and for cardiovascular causes (78 vs. 130; P = .02).

In a separate study, researchers conducted an open-label trial of 237 patients with New York Heart Association (NYHA) class II-IV heart failure who were randomized to torsemide or furosemide. They found that a significantly higher percentage of patients in the torsemide group improved by one or more NYHA heart failure class, compared with those in the furosemide group (40%; P = .001 vs. 31%; P = .3). Moreover, patients treated with furosemide had more restrictions of daily life at 9 months, compared with those treated with torsemide (P < .001).

A separate, open-label, nonrandomized, postmarketing surveillance trial also found benefits of torsemide over furosemide or other agents used for patients with NYHA class III and IV heart failure. Patients treated with torsemide had a lower total mortality, compared with those treated with furosemide or other agents (2.2% vs. 4.5%, respectively; P < .05) as well as a lower cardiac mortality (1.4% vs. 3.5%; P < .05). They were also more likely to improve by one or more heart failure class (46% vs. 37%; P < .01) and less likely to have potassium levels less than 3.5 mEq/L or greater than 5.0 mEq/L (13% vs. 18%; P = .01).

According to Dr. Breu, meta-analyses of this topic consistently show that the NYHA class improved more with torsemide than with furosemide. “Some meta-analyses find a mortality benefit, while others find a readmissions benefit,” he said. “None of them show a benefit of furosemide over torsemide.”

A second reason to use torsemide as a first-line treatment for heart failure is that it has superior pharmacokinetics/dynamics, compared with furosemide. “We’ve all heard that furosemide has variable bioavailability,” said Dr. Breu, who also deputy editor of the Journal of Hospital Medicine’s “Things We Do For No Reason” article series. “Torsemide and bumetanide are much more reliably absorbed, partially because they are not affected by food, whereas furosemide is. That could be potentially problematic for patients who take their diuretic with meals. The fact that torsemide has less renal clearance is a benefit, because patients with heart failure have changing renal function.” In addition, the half-life of torsemide is 3-4 hours and the duration of action is 12 hours, “which are both longer than those for furosemide or bumetanide,” he added.

He also pointed out that torsemide has been shown to block the aldosterone receptor in vitro and in rat models – an effect that has not been observed with other loop diuretics. A randomized trial of patients with chronic heart failure found that levels of renin and aldosterone increased more with torsemide, compared with furosemide, supporting the hypothesis of aldosterone receptor blockade.

A third main reason to use torsemide as your go-to for heart failure has to do with its purported antifibrotic effects, “so that it could be more than a diuretic,” Dr. Breu said. “In heart failure, myocardial fibrosis occurs from increased collagen synthesis and turnover. Aldosterone has been shown to play a role in this myocardial fibrosis. Spironolactone has been shown to mitigate this to some extent. If torsemide acts a little like spironolactone, maybe that could explain some of the long-term effects that we see in these studies.”

A study supporting this notion found that torsemide but not furosemide reduced levels of serum carboxyl-terminal peptide of procollagen type I, which is associated with exaggerated myocardial deposition of collagen type I fibers in cardiac diseases.

Going forward, a study known as TRANSFORM-HF, which is currently recruiting about 6,000 patients, should bring more clarity to the topic. The primary objective is to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in patients with heart failure who are hospitalized. The estimated completion is mid-2022.

Dr. Breu and Dr. Feldman reported having no relevant financial disclosures.

When starting a new loop diuretic for a patient with heart failure, strongly consider torsemide over furosemide, Anthony C. Breu, MD, advised at SHM Converge, the annual conference of the Society of Hospital Medicine.

“Whether or not you take a patient who’s already on furosemide and you make the switch to torsemide is a little bit tougher for me to advocate, though that has happened in clinical trials,” said Dr. Breu, assistant professor of medicine at Harvard Medical School, Boston, who spoke May 5 at the Converge session “Things We Do for No Reason.” He co-presented the session with Leonard Feldman, MD, SFHM, director of the Osler Medical Residency Urban Health Track and associate professor at Johns Hopkins Medicine, Baltimore.

“If you consider doing this it would make sense to do so concert with the outpatient primary doctor and the outpatient cardiologist,” Dr. Breu said. “But in my review of the literature, it’s at least worth having these discussions, particularly for a patient who has multiple readmissions for heart failure. That may be a time to pause and ask: ‘Could torsemide be of benefit here?’ ”

In Dr. Breu’s opinion, there are at least three reasons why consider torsemide should be considered a first-line treatment for heart failure. For one thing, the current evidence says so. In a trial published in 2001, researchers randomized 234 patients with heart failure to receive torsemide or furosemide for 1 year. The percentage of patients who had one or more hospital readmissions was lower among those who received torsemide, compared with those who received furosemide in the torsemide group for heart failure (17% vs. 32%, respectively; P < .01) and for other cardiovascular causes (44% vs. 59%; P = .03). In addition, the number of total admissions was numerically lower for patients in the torsemide group, compared with the furosemide group for heart failure (23 vs. 61; P < .01) and for cardiovascular causes (78 vs. 130; P = .02).

In a separate study, researchers conducted an open-label trial of 237 patients with New York Heart Association (NYHA) class II-IV heart failure who were randomized to torsemide or furosemide. They found that a significantly higher percentage of patients in the torsemide group improved by one or more NYHA heart failure class, compared with those in the furosemide group (40%; P = .001 vs. 31%; P = .3). Moreover, patients treated with furosemide had more restrictions of daily life at 9 months, compared with those treated with torsemide (P < .001).

A separate, open-label, nonrandomized, postmarketing surveillance trial also found benefits of torsemide over furosemide or other agents used for patients with NYHA class III and IV heart failure. Patients treated with torsemide had a lower total mortality, compared with those treated with furosemide or other agents (2.2% vs. 4.5%, respectively; P < .05) as well as a lower cardiac mortality (1.4% vs. 3.5%; P < .05). They were also more likely to improve by one or more heart failure class (46% vs. 37%; P < .01) and less likely to have potassium levels less than 3.5 mEq/L or greater than 5.0 mEq/L (13% vs. 18%; P = .01).

According to Dr. Breu, meta-analyses of this topic consistently show that the NYHA class improved more with torsemide than with furosemide. “Some meta-analyses find a mortality benefit, while others find a readmissions benefit,” he said. “None of them show a benefit of furosemide over torsemide.”

A second reason to use torsemide as a first-line treatment for heart failure is that it has superior pharmacokinetics/dynamics, compared with furosemide. “We’ve all heard that furosemide has variable bioavailability,” said Dr. Breu, who also deputy editor of the Journal of Hospital Medicine’s “Things We Do For No Reason” article series. “Torsemide and bumetanide are much more reliably absorbed, partially because they are not affected by food, whereas furosemide is. That could be potentially problematic for patients who take their diuretic with meals. The fact that torsemide has less renal clearance is a benefit, because patients with heart failure have changing renal function.” In addition, the half-life of torsemide is 3-4 hours and the duration of action is 12 hours, “which are both longer than those for furosemide or bumetanide,” he added.

He also pointed out that torsemide has been shown to block the aldosterone receptor in vitro and in rat models – an effect that has not been observed with other loop diuretics. A randomized trial of patients with chronic heart failure found that levels of renin and aldosterone increased more with torsemide, compared with furosemide, supporting the hypothesis of aldosterone receptor blockade.

A third main reason to use torsemide as your go-to for heart failure has to do with its purported antifibrotic effects, “so that it could be more than a diuretic,” Dr. Breu said. “In heart failure, myocardial fibrosis occurs from increased collagen synthesis and turnover. Aldosterone has been shown to play a role in this myocardial fibrosis. Spironolactone has been shown to mitigate this to some extent. If torsemide acts a little like spironolactone, maybe that could explain some of the long-term effects that we see in these studies.”

A study supporting this notion found that torsemide but not furosemide reduced levels of serum carboxyl-terminal peptide of procollagen type I, which is associated with exaggerated myocardial deposition of collagen type I fibers in cardiac diseases.

Going forward, a study known as TRANSFORM-HF, which is currently recruiting about 6,000 patients, should bring more clarity to the topic. The primary objective is to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in patients with heart failure who are hospitalized. The estimated completion is mid-2022.

Dr. Breu and Dr. Feldman reported having no relevant financial disclosures.

When starting a new loop diuretic for a patient with heart failure, strongly consider torsemide over furosemide, Anthony C. Breu, MD, advised at SHM Converge, the annual conference of the Society of Hospital Medicine.

“Whether or not you take a patient who’s already on furosemide and you make the switch to torsemide is a little bit tougher for me to advocate, though that has happened in clinical trials,” said Dr. Breu, assistant professor of medicine at Harvard Medical School, Boston, who spoke May 5 at the Converge session “Things We Do for No Reason.” He co-presented the session with Leonard Feldman, MD, SFHM, director of the Osler Medical Residency Urban Health Track and associate professor at Johns Hopkins Medicine, Baltimore.

“If you consider doing this it would make sense to do so concert with the outpatient primary doctor and the outpatient cardiologist,” Dr. Breu said. “But in my review of the literature, it’s at least worth having these discussions, particularly for a patient who has multiple readmissions for heart failure. That may be a time to pause and ask: ‘Could torsemide be of benefit here?’ ”

In Dr. Breu’s opinion, there are at least three reasons why consider torsemide should be considered a first-line treatment for heart failure. For one thing, the current evidence says so. In a trial published in 2001, researchers randomized 234 patients with heart failure to receive torsemide or furosemide for 1 year. The percentage of patients who had one or more hospital readmissions was lower among those who received torsemide, compared with those who received furosemide in the torsemide group for heart failure (17% vs. 32%, respectively; P < .01) and for other cardiovascular causes (44% vs. 59%; P = .03). In addition, the number of total admissions was numerically lower for patients in the torsemide group, compared with the furosemide group for heart failure (23 vs. 61; P < .01) and for cardiovascular causes (78 vs. 130; P = .02).

In a separate study, researchers conducted an open-label trial of 237 patients with New York Heart Association (NYHA) class II-IV heart failure who were randomized to torsemide or furosemide. They found that a significantly higher percentage of patients in the torsemide group improved by one or more NYHA heart failure class, compared with those in the furosemide group (40%; P = .001 vs. 31%; P = .3). Moreover, patients treated with furosemide had more restrictions of daily life at 9 months, compared with those treated with torsemide (P < .001).

A separate, open-label, nonrandomized, postmarketing surveillance trial also found benefits of torsemide over furosemide or other agents used for patients with NYHA class III and IV heart failure. Patients treated with torsemide had a lower total mortality, compared with those treated with furosemide or other agents (2.2% vs. 4.5%, respectively; P < .05) as well as a lower cardiac mortality (1.4% vs. 3.5%; P < .05). They were also more likely to improve by one or more heart failure class (46% vs. 37%; P < .01) and less likely to have potassium levels less than 3.5 mEq/L or greater than 5.0 mEq/L (13% vs. 18%; P = .01).

According to Dr. Breu, meta-analyses of this topic consistently show that the NYHA class improved more with torsemide than with furosemide. “Some meta-analyses find a mortality benefit, while others find a readmissions benefit,” he said. “None of them show a benefit of furosemide over torsemide.”

A second reason to use torsemide as a first-line treatment for heart failure is that it has superior pharmacokinetics/dynamics, compared with furosemide. “We’ve all heard that furosemide has variable bioavailability,” said Dr. Breu, who also deputy editor of the Journal of Hospital Medicine’s “Things We Do For No Reason” article series. “Torsemide and bumetanide are much more reliably absorbed, partially because they are not affected by food, whereas furosemide is. That could be potentially problematic for patients who take their diuretic with meals. The fact that torsemide has less renal clearance is a benefit, because patients with heart failure have changing renal function.” In addition, the half-life of torsemide is 3-4 hours and the duration of action is 12 hours, “which are both longer than those for furosemide or bumetanide,” he added.

He also pointed out that torsemide has been shown to block the aldosterone receptor in vitro and in rat models – an effect that has not been observed with other loop diuretics. A randomized trial of patients with chronic heart failure found that levels of renin and aldosterone increased more with torsemide, compared with furosemide, supporting the hypothesis of aldosterone receptor blockade.

A third main reason to use torsemide as your go-to for heart failure has to do with its purported antifibrotic effects, “so that it could be more than a diuretic,” Dr. Breu said. “In heart failure, myocardial fibrosis occurs from increased collagen synthesis and turnover. Aldosterone has been shown to play a role in this myocardial fibrosis. Spironolactone has been shown to mitigate this to some extent. If torsemide acts a little like spironolactone, maybe that could explain some of the long-term effects that we see in these studies.”

A study supporting this notion found that torsemide but not furosemide reduced levels of serum carboxyl-terminal peptide of procollagen type I, which is associated with exaggerated myocardial deposition of collagen type I fibers in cardiac diseases.

Going forward, a study known as TRANSFORM-HF, which is currently recruiting about 6,000 patients, should bring more clarity to the topic. The primary objective is to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in patients with heart failure who are hospitalized. The estimated completion is mid-2022.

Dr. Breu and Dr. Feldman reported having no relevant financial disclosures.