Imagine this clinical scenario: a six-year-old male neutered Cocker Spaniel presents to you as an emergency, with tachypnoea, dyspnoea, a grade III/VI systolic heart murmur and a recent history of exercise intolerance. After initial stabilisation, you have diagnosed stage C degenerative mitral valve disease (DMVD) and plan to start this patient on appropriate oral medication, which will include a diuretic. Typically, furosemide will be used, but is there any evidence to suggest that the use of torasemide carries any benefits as a first-line diuretic?
The evidence
Five prospective randomised studies were critically appraised, though only one study was blinded. Four papers had small sample sizes (less than 10) and the length of the studies was generally a couple of weeks.
A paper by Chetboul et al. (2017) investigated 366 dogs with congestive heart failure (CHF) due to DMVD, split into two groups. Group one included dogs that presented with their first CHF episode who needed a diuretic or dogs that had existing CHF and needed a change in diuretic dose due to deterioration. Dogs in group two had a previous episode of CHF and were now stable. All dogs received either furosemide (n=186) or torasemide (n=180) for three months. There were two studies in this paper, with the second study reducing doses of torasemide. The hypothesis was that treatment of group one was expected to improve their clinical condition, while treatment of group two was expected to be able to maintain their condition.
The composite cardiac endpoint was reached in a shorter time-period in the furosemide group than the torasemide group, which was statistically significant
At the end of study one, 63 percent (47/75) of dogs receiving torasemide had treatment success, compared to 55 percent (42/76) of dogs receiving furosemide. For study two, 60 percent (63/105) of dogs receiving torasemide had treatment success over 59 percent (65/110) of dogs receiving furosemide. The composite cardiac endpoint was reached in a shorter time-period in the furosemide group than the torasemide group, which was statistically significant. The torasemide group had a statistically significant higher number of adverse effects, including polyuria/polydipsia.
In a study by Peddle et al. (2012), seven dogs were enrolled and had already been receiving furosemide for the preceding 14 days. At enrolment, dogs were randomly assigned to two groups: either continuing existing furosemide dose (n=4) or changing to torasemide at an equivalent dose (n=3). On day seven there was a crossover of groups, and the study ended on day 14. The results showed no dog in either group developed CHF, either clinically or radiographically, at any time. There were increases in creatinine, BUN, phosphorus, carbon dioxide, albumin and the anion gap following the torasemide treatment, which were all significant.
Uechi et al. (2003) studied 10 healthy dogs, split into a control group (n=5) and a second group who underwent surgery to induce mitral regurgitation. The study was performed six to eight months post-operatively. Each dog (from both groups) randomly received placebo, furosemide and torasemide for seven days, with each treatment period separated by a 14-day interval. The results showed that no dog developed CHF. Mean analysis of urine at day seven revealed dogs receiving torasemide had a significantly decreased urinary potassium excretion compared to day one in both groups.
Compared to placebo, only long-term administration of torasemide statistically significantly increased urine volume but compared to furosemide, short- and long-term administrations of torasemide increased urine volume, also significantly
Hori et al. (2007) studied eight healthy dogs, randomised to receive either placebo, furosemide or torasemide for 14 days. Each dog received all three treatments for 14 days, with at least a seven-day interval between treatments. Short-term administration (one day) of furosemide and torasemide significantly increased urine volume compared to baseline (pre-treatment) and placebo. Long-term (14 days) administration of furosemide and torasemide decreased urine specific gravity significantly. Compared to placebo, only long-term administration of torasemide statistically significantly increased urine volume but compared to furosemide, short- and long-term administrations of torasemide increased urine volume, also significantly.
In a study by Potter et al. (2019), six healthy dogs randomly received either placebo, furosemide (2mg/kg) and torasemide (0.1mg/kg). All three treatments were given PO every 12 hours for 10 days, with a 10-day washout period between each treatment. In all dogs, there were no significant differences within or between treatment groups for BUN, sodium or potassium. Hypochloraemia was present in both diuretic treatment groups when compared to placebo.
Conclusion
Overall, in view of the strength of the evidence and outcomes of the studies, no clear benefit for the use of torasemide over furosemide as a first-line diuretic for dogs with congestive heart failure can be drawn. Of the five papers examined, only one paper (Chetboul et al., 2017) had a reasonable population number, with the other studies including 10 dogs or fewer.
Further research involving well-powered studies into the long-term safety of torasemide for the treatment of animals in chronic CHF would be beneficial
Within human medicine, there are studies demonstrating that, compared to furosemide, torasemide can reduce morbidity and mortality associated with CHF failure (Cosín et al., 2002). Given that the studies found some positive findings of torasemide, such as reduced diuretic resistance, reduced cardiac remodelling and a potassium-sparing nature, further research involving well-powered studies into the long-term safety of torasemide for the treatment of animals in chronic CHF would be beneficial.
The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence.
