A Diuretic Flop in Heart Failure

Volume 24, Issue 1

Loop diuretics have been a cornerstone therapy for patients with heart failure for decades. The historical first-line loop diuretic is furosemide, based on its lower cost when bumetanide and torsemide were still branded drugs. While the loop diuretics have never proven to reduce mortality rates in patients with heart failure, over 90% of patients with heart failure still require loop diuretic therapy to maintain euvolemia. 

Recent preclinical evidence has suggested torsemide may have favorable anti-inflammatory and anti-remodeling properties in patients with heart failure. This drug also has some pharmacokinetic advantages over furosemide, including improved bioavailability and a longer half-life. 

In this week’s issue of Talking Therapeutics, we explore a landmark trial that evaluated clinical endpoints between torsemide and furosemide in patients with recently decompensated heart failure. 

Point 1: No Real Benefit for Torsemide

The TRANSFORM-HF trial randomized nearly 3000 patients who were hospitalized with heart failure (regardless of ejection fraction) to a regimen of oral torsemide or oral furosemide. The primary outcome was all-cause mortality in a time-to-event analysis, and researchers also assessed all-cause mortality or all-cause hospitalization and total hospitalizations over 12 months. 

Over a median of roughly 18 months of follow up, 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group died (hazard ratio, 1.02 [95% CI, 0.89-1.18]. There was no difference in the rates of rehospitalization for heart failure or any of the secondary endpoints. The findings were also consistent across all prespecified subgroups and across the spectrum of ejection fraction. 

Point 2: Stick to Other Therapies

Recent studies demonstrated the SGLT2 inhibitors can be used safely in patients with acute heart failure. These agents may lead to more effective decongestion and may reduce the risk of rehospitalization, making them a great option to add to loop diuretic therapy for patients hospitalized with heart failure. There was also a recent study indicating that adding acetazolamide therapy to loop diuretics may improve outcomes in patients hospitalized with heart failure. 

Based on the results of the TRANSFORM-HF trial, adding either SGLT2 therapy or acetazolamide to furosemide would be preferred over switching from furosemide to torsemide.