Torsemide versus Furosemide: No Difference after All?

Although various loop diuretics have long been considered equivalent for treating congestive heart failure (CHF), recent, small studies have suggested that torsemide may be superior to furosemide for decreasing mortality and hospitalization rates, possibly by reducing renin-angiotensin-aldosterone system activation and myocardial fibrosis (1). The Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) trial was a multi-center, open-label, pragmatic trial in which 2859 patients hospitalized for CHF were randomized to either torsemide or furosemide and were followed for up to 1 year after discharge (2). Based on previous data, the authors powered the trial to detect a 20% reduction in mortality with torsemide.

Eligible patients were those hospitalized with worsening chronic CHF or a new diagnosis of CHF, plus ejection fraction ≤40% or elevated natriuretic peptide levels. Patients were discharged with either torsemide or a bioequivalent dose of furosemide (a ratio of 1 mg torsemide to 2–4 mg furosemide). Those with end stage kidney disease were excluded from the study. Furthermore, the approximately 35% of patients with chronic kidney disease (CKD) included mostly mild CKD, with a mean estimated glomerular filtration rate of 59 mL/min/1.73 m². More than 90% of patients were adherent to diuretics at 6 months, but patients in the torsemide group had been prescribed a higher dose than those in the furosemide group after only 1 month. The primary end point of all-cause mortality was roughly identical at 26% in both torsemide and furosemide groups. All-cause hospitalization rates were similar. On the heels of recent advances in CHF management, it is no surprise that a hint of torsemide's preferential benefit sparked intense interest. The rise of the sodium-glucose cotransporter-2 inhibitors (SGLT2is), for example, is largely due to their proven value in reducing cardiovascular mortality, CHF hospitalization, and CKD progression (3, 4). In the TRANSFORM-HF study, curiously, only 6% of patients were prescribed SGLT2i, 19% sacubitril-valsartan, 35% mineralocorticoid receptor blockers, and 40% angiotensin-converting enzyme inhibitors. The aggregate enrollment of patients with both a reduced and preserved ejection fraction possibly accounts for this low utilization rate of evidence-based medical therapy.

So, how does TRANSFORM-HF impact the practice of nephrology? As cardiorenal syndrome is a major cause of acute kidney injury in hospitalized patients, both cardiologists and nephrologists target effective decongestion, which is associated with improved post-discharge outcomes. The current standard of care for patients hospitalized with acute, decompensated CHF includes conversion of oral to intravenous loop diuretics with a stepwise increase in dose, administered as either bolus or continuous infusion (5, 6). Diuretic resistance should be addressed by increasing the loop diuretic dose or adding a thiazide-type diuretic. Although TRANSFORM-HF did not show significant differences in mortality or rehospitalization for patients with CHF who were prescribed torsemide versus furosemide, further investigation into the potential differences among specific drugs within diuretic classes may yet uncover unexpected benefits and is worth examining.