Heart failure & cardiomyopathies
Comparative Strategies to Overcome Diuretic Resistance in Heart Failure: A Network Meta-Analysis
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 adults19 randomized controlled trials (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
Methodological detailsRCTs
- RCTs
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
| OR (95% CI) | ||
|---|---|---|
| DapagliflozinReduced heart failure hospitalizations | 0.15 (0.03–0.73) | |
| EmpagliflozinReduced heart failure hospitalizations | 0.19 (0.04–0.94) | |
| 0.050.21520Odds ratio (log scale) |
Follow-up-adjusted mortality (incidence rate ratios)
- Neutral to favorable but imprecise and consistent in ≤60-day sensitivity analyses
Safety
Acute kidney injury
| OR (95% CI) | ||
|---|---|---|
| High-dose loop diureticsIncreased acute kidney injury | 2.27 (1.20–4.30) | |
| HydrochlorothiazideIncreased acute kidney injury | 4.14 (2.03–8.42) | |
| 0.10.31310Odds ratio (log scale) |
Original publication
Comparative Strategies to Overcome Diuretic Resistance in Heart Failure: A Network Meta-Analysis. JACC Adv. Published 23 February 2026. doi:10.
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