Episode 194: 194. Heart Failure and Diuretics

SUMMARY--

What diuretic do you usually write for during CHF hospitalizations?? If you said furosemide you are not alone

One in a study in JACC 2013 looked at HF hospitalizations in 2009 and 2010 – In total 251,472 patients got a loop diuretic during their hospitalization and almost 87% got just furosemide, about 3% only got bumex, while only 0.4 received only torsemide.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038646/#R11

What is the difference between bumetanide and furosemide?

Nothing—or at least nothing we care about. No hard outcomes, no patient oriented outcomes.

Bumetanide is stronger—An article from 2015 in American Heart Journal states bumetanide is about 40 times stronger than furosemide- thus at times you might have your sphincter tighten when you go to write for 120-160mg of furosemide but feel comfortable writing for 3-4mg of bumex. They also discuss how bumetanide also appears to have a higher more consistent bioavailability at around 80-100% while furosemide seems to range from 10-100% depending on the study. Conclusion: the benefits for bumetanide are there in theory but no hard outcomes that I could find.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346710/

What about torsemide??

The bioavailability of torsemide is 76% to 96% and as I mentioned before furosemide hangs out around 10% to 100%. In addition, furosemide bioavailability can decrease by up to 30% with food while torsemide is not affected by food consumption.

https://oce.ovid.com/article/00006562-199701000-00009

https://pubmed.ncbi.nlm.nih.gov/3709617/

HOWEVER, no patient cares about bioavailability they want to know if they will live longer or live better (patient oriented outcomes)??

First paper- 2001 Nov;111(7):513-20.

American Journal of Medicine we have a paper titled

“Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure”

This was open-label trial of 234 patients who were randomized to torsemide or furosemide and followed for 1 yr. The outcome was heart failure readmissions and it occurred significantly less in the torsemide group, only 17% of the time compared to 32% in the furosemide group. https://pubmed.ncbi.nlm.nih.gov/11705426/

That is almost a 50% relative reduction for heart failure hospitalization at one year! This is an outcome both patients and hospitalist would love to see!

Second paper-

In 2002- a year later-

European Journal of Heart Failure a paper titled

Torasemide in chronic heart failure: results of the TORIC study

This was the published results of the ‘TOrasemide In Congestive Heart Failure (TORIC)’ study- It was an open-label, non-randomised, post-marketing surveillance trial. The individuals who were prescribed torsemide on top of their other CHF medications for 12 months had almost a 50% relative reduction in mortality!! That may not seem like a lot but remember this is only 12 months and the outcome was DEATH! In absolute terms roughly 2% of participants died in the torsemide group and 4% died in the furosemide/other diuretic group. PLUS, those in the torsemide group also had an improvement in their NYHA functional heart class.

https://pubmed.ncbi.nlm.nih.gov/12167392/

Finally, there is a meta-analysis from 2019 in Journal of Cardiovascular Medicine titled

Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis

Which looked at a total of 14 randomized trials and just over 8000 pts and found torsemide to have both fewer heart failure hospitalizations and those individuals taking torsemide were more likely to have an improvement in their new york heart association class but they didnt find a difference in mortality.

https://pubmed.ncbi.nlm.nih.gov/30950982/

Currently there is 6000 pt randomized trial that is underway and will be done in august 2023.

https://clinicaltrials.gov/ct2/show/NCT03296813

That is it, that is all that I could find!!!!

However, with the evidence clearly in favor of torsemide, why have I never even considered it before doing this lecture??

Likely 2 problems

1) It is what we have always done and it is hard to change practice! Furosemide was approved for medical use in 1964.Torsemide was approved in 1993. We as providers get into a rut, the next drug we prescribe is likely to be one of the most recent drugs we prescribed. If you show me the last 10 hypertension medications you prescribed then with almost 90-100% certainty I can guess the next one that you are going to prescribe.

2) There use to be a cost issue when furosemide was generic and torsemide was not. However, now these are both old drugs and per goodrx down here in Florida they only differ by about 1.50$ per month, but we are saving hospitalizations which cost 1000$.

A paper from 2000 in Pharmacoeconomics titled “Healthcare costs of patients with heart failure treated with torasemide or furosemide” found torsemide average hospitalization cost per patient each year was $1000 while those in the furosemide group had an average cost of $1500 dollars, and this was back when torsemide wasn’t nearly as cheap as it is now.

I know I have given you a lot of numbers but a good take away is-

Torsemide compared to furosemide has a NNT at 10.5 months to prevent a heart failure hospitalization around 6!!!

https://pubmed.ncbi.nlm.nih.gov/10977385/

https://www.medscape.com/viewarticle/771976_8

Even if the number is off a little because of study design flaws like blinding and sample size the evidence does appear to continually point the direction of benefit towards torsemide. Even if you doubled it, a NNT of 12, it is still really good.