Diuretic resistance risk and the efficacy of torsemide vs furosemide: a post-hoc analysis of the TRANSFORM-HF trial

BACKGROUND/AIMS: Among hospitalized patients with HF, diuretic resistance is associated with residual congestion, poor health status, and increased risk of HF hospitalization and mortality in the post-discharge period. The TRANSFORM-HF trial demonstrated no difference between torsemide and furosemide on clinical outcomes or quality-of-life following HF hospitalization. We assessed the association between diuretic resistance risk, assessed using the BAN-ADHF score, with risk of adverse outcomes among participants of the TRANSFORM-HF trial, and whether diuretic resistance risk modified the treatment effects of torsemide versus furosemide. METHODS: This post-hoc analysis of TRANSFORM-HF included participants randomized to torsemide or furosemide who survived to discharge with available BAN-ADHF scores. High diuretic resistance risk was defined as BAN-ADHF score ≥12 during index hospitalization. Associations of diuretic resistance risk with 12-month all-cause mortality, all-cause hospitalization, and quality of life (KCCQ-CSS) were assessed using adjusted Cox models, and linear mixed-effects models, respectively. Treatment effect modification was assessed via interaction terms between randomized treatment and diuretic resistance risk status (high vs low). RESULTS: Among 2,421 participants (age:65 years, 62.9% male), 512 (21%) had high diuretic resistance risk. High diuretic resistance risk was associated with increased risk of all-cause mortality (aHR[95%CI]: 1.79[1.45-2.21], p<0.001), all-cause hospitalization (aHR: 1.34[1.15-1.55], p<0.001), and lower 12-month KCCQ-CSS improvement (-3.4 points, p=0.037). Diuretic resistance risk status did not modify the treatment effect of torsemide vs furosemide on all-cause mortality (pinteraction=0.54), all-cause hospitalization (pinteraction=0.74), or quality-of-life on follow-up (pinteraction>0.05 at each timepoint). CONCLUSIONS: Among patients discharged after HF hospitalization, higher diuretic resistance risk, assessed by the BAN-ADHF score, is associated with higher risk of mortality, HF hospitalization, and worse quality-of-life. Diuretic resistance risk status did not modify the treatment effects of torsemide versus furosemide.