Torsemide versus furosemide after acute decompensated heart failure: a retrospective observational study

Heart failure (HF) is considered the most common cause of hospital admissions in the United States leading to approximately 1.1 million hospitalizations annually [1]. Loop diuretics are recommended by clinical practice guidelines, including the latest American College of Cardiology Foundation/American Heart Association Heart Failure report ACCF/AHA (2013) (Class IB) and the European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (2016) (Class IB), for treating volume overload and relieving symptoms of congestion among patients with acute decompensated heart failure (ADHF) with left ventricular dysfunction [2, 3].

Initially, patients presenting with acute decompensation of heart failure and already using furosemide should receive an intravenous furosemide dose that is at least equal to the oral home dose to treat fluid retention [2, 3]. Once fluid retention has resolved, patients will be discharged on oral diuretics to prevent the recurrence of volume overload [2]. Upon discharge, patients may receive higher doses of furosemide than their previous home doses to maintain euvolemia achieved with intravenous furosemide during the hospital stay, due to the low oral bioavailability of furosemide that is about 50% [4]. Torsemide, however, has increased bioavailability (> 80%) and a longer half-life compared with furosemide [4], promoting its use following ADHF in patients previously using furosemide or other diuretics [5]. Moreover, torsemide has protective effects on ventricular structure and beneficial effects on the neurohormonal axis [6]. Nevertheless, data guiding diuretic dosing after ADHF and the association with subsequent outcomes are limited. A number of clinical trials that compared torsemide versus furosemide in HF suggested improved morbidity and mortality with torsemide; however, these studies included patients with chronic heart failure without a recent hospitalization for ADHF and did not evaluate switching furosemide to torsemide versus optimizing the dose of furosemide upon discharge [7, 8]. Therefore, this retrospective observational study aims to evaluate the effectiveness of switching furosemide to torsemide versus increasing furosemide dose upon discharge among HF patients admitted with ADHF and to determine the predictors of switching furosemide to torsemide upon discharge.

In this retrospective observational study, we found that switching from furosemide to the more potent diuretic torsemide, compared to optimizing the dose of furosemide, following ADHF did not reduce the hospitalization due to HF within 1 month or 6 months of discharge. Since torsemide is a more potent loop diuretic with higher bioavailability and less erratic absorption in patients with HF that retains its pharmacodynamic effects regardless of the HF severity compared to furosemide [4, 5, 10], it was hypothesized that changing furosemide to torsemide would result in more favorable clinical outcomes than increasing the dose of furosemide following ADHF among patients already using furosemide prior to admission.

A systematic review and a meta-analysis of two randomized clinical trials that compared torsemide to furosemide in HF suggested that torsemide improved HF hospitalization (relative risk [RR] = 0.41, 95% CI 0.28–0.61, p < 0.0001) and cardiovascular mortality (RR = 0.86 95% Cl 0.53–1.39, p = 0.54); however, the two trials included in the analysis involved patients with chronic heart failure rather than ADHF [11]. Moreover, a large retrospective study (n = 4580) conducted at a tertiary center assessed the clinical outcomes, including hospitalization and mortality following admission for HF showed that torsemide use compared to furosemide was associated with significant increase in 30-day HF hospitalization (OR = 1.52, 95% CI 1.11–2.09, p = 0.0099); however, after adjustment for age, gender, chronic kidney disease, creatinine, ejection fraction, right ventricular size, aortic stenosis, mitral stenosis, tricuspid regurgitation, aldosterone antagonists, and ACE-inhibitors, torsemide use was not associated with increased HF hospitalization (aOR = 1.29, 95 CI 0.91–1.83, p = 0.1607). Nevertheless, the study neither evaluated changing furosemide to torsemide nor conducted an analysis of the patients already using a loop diuretic prior to admission [12].

Despite clinical and pharmacokinetic evidence favoring torsemide over furosemide in HF, our study did not demonstrate reductions in HF hospitalization at 1 or at 6 months with torsemide. However, our study answered a crucial clinical question of whether switching furosemide to a more potent diuretic (torsemide) following ADHF without increasing the dose would reduce HF-related hospitalization compared to increasing the furosemide dose. In our study, patients in the furosemide arm were discharged on double the baseline dose, while patients in torsemide arm were switched to torsemide at doses equivalent to the baseline furosemide dose and there was no difference between the two approaches in terms of clinical outcomes. Therefore, switching furosemide to an equivalent dose of torsemide may be as effective as optimizing the dose of furosemide after ADHF, which may represent a therapeutic advantage for torsemide.

In the present study, we investigated the predictors of torsemide use. Although these associations do not necessarily indicate causality, they might reflect a trend in prescribing pattern or highlight some indicators of disease progression to a stage where furosemide does not achieve the desired level of euvolemia. Interestingly, similar to Mentz et al., our study identified the use of aldosterone antagonists and higher EF as positive predictors of torsemide use in HF (OR = 1.97, 95% CI 1.59–2.44, p = < 0.0001; OR = 1.10, 95% CI = 1.07–1.14, p = < 0.0001; respectively), and increased age along with ACE inhibitor use as negative predictors of torsemide use (OR = 0.92, 95% CI 0.89–0.96, p = < 0.0001; OR = 0.78, 95% Cl 0.63–0.95, p = 0.015; respectively) [12].

This was a retrospective observational study which is susceptible to potential limitations. First, data were collected from the medical records with the expectation of missing some essential clinical information. Second, the study did not evaluate the impact on mortality of switching torsemide to furosemide versus optimizing the furosemide dose. However, we did not expect a difference in mortality due to lack of difference in placebo-controlled studies of furosemide. Third, the results were adjusted for clinically significant variables; however, there is a potential for other measured or unmeasured variables to influence the results. Forth, the number of torsemide users and optimized furosemide users were relatively small, which might have affected the robustness of the results. Nevertheless, this retrospective observational study aimed to answer a clinically important and challenging question that is faced by clinicians in daily practice, and it could serve as a preliminary indicator for future prospective studies to assess the impact of torsemide versus furosemide following ADHF on cardiovascular outcomes.

In conclusion, switching furosemide to an equivalent dose of torsemide after ADHF was not associated with reduced HF-related hospitalization compared to optimizing the furosemide dose. Therefore, following ADHF, clinicians can follow either approach. However, larger prospective clinical trials are needed to confirm the findings of this study and to assess other important cardiovascular outcomes, including mortality.