Heart failure & cardiomyopathiesMeta-analysis

Comparative Strategies to Overcome Diuretic Resistance in Heart Failure

JACC AdvPublished

  • random-effects network meta-analysis of randomized controlled trials (RCTs)

Authors' conclusion

In HF with diuretic resistance, sodium-glucose cotransporter 2 inhibitors may lower rehospitalization with a favorable renal profile, whereas nephron-segment add-ons enhance short-term decongestion but warrant AKI/electrolyte monitoring; rankings are exploratory, and choices should emphasize absolute effects and 95% CIs.

Study context

Population
Adults with heart failure and diuretic resistance
Participants
9,685 Nineteen RCTs
Comparison
pharmacologic strategies for diuretic resistance in heart failure (HF)
Outcome
72-h urine output and standardized 72-h weight
Follow-up
72 hours

Pooled result

As reported in the abstract

SMD (95% CI)
hydrochlorothiazide72-hour weight change; greatest standardized reductions
1.33(0.49–2.18)
tolvaptan72-hour weight change; greatest standardized reductions
0.69(0.09–1.29)

MD, mL

tolvaptan vs low-dose loop diuretics · 72-hour urine output increased
1,840 (95% CI 441–3,240)
low-dose loop plus tolvaptan vs low-dose loop diuretics · 72-hour urine output increased
1,643 (95% CI 53–3,234)

Further pooled results

heart failure hospitalizations

ComparisonOR (95% CI)
Dapagliflozin · reduced heart failure hospitalizations0.15 (0.03–0.73)
empagliflozin · reduced heart failure hospitalizations0.19 (0.04–0.94)

Follow-up-adjusted mortality (incidence rate ratios)

neutral to favorable but imprecise and consistent in ≤60-day sensitivity analyses

Safety

acute kidney injury

ComparisonOR (95% CI)
High-dose loop diuretics · increased acute kidney injury2.27 (1.20–4.30)
hydrochlorothiazide · increased acute kidney injury4.14 (2.03–8.42)

Original publication

Comparative Strategies to Overcome Diuretic Resistance in Heart Failure. JACC Adv. Published 23 February 2026. doi:10.1016/j.jacadv.2026.102617

Summarised from the published abstract; every number is checked against it