Diuretic strategies in acute heart failure: a systematic review and network meta-analysis of randomized clinical trials.

Aims: Several diuretic strategies, including furosemide iv boluses (FB) or continuous infusion (FC), are used in acute heart failure (AHF).

Methods And Results: We systematically searched phase 3 randomized clinical trials (RCTs) evaluating diuretic regimens in admitted AHF patients within 48 hours and irrespective of clinical stabilization. We calculated the odds ratio (OR) of FC or FB plus another diuretic (sequential nephron blockade, SNB) compared to FB alone on 24-hour weight loss (WL) and worsening renal function (WRF), with a random-effects model with inverse variance weighting. Urine output, hypokalaemia, hyponatremia, and all-cause mortality/rehospitalization were secondary endpoints.In 25 selected RCTs (7,149 patients, mean age 68.9±8.7 years, mean LVEF 38.2±10.7%), FC (OR 1.55 [95% confidence interval 1.39-1.63], FB plus tolvaptan (OR 1.57 [1.39-1.77]), FB plus SGLT2i (OR 1.23 [1.06-1.42]), and FB plus thiazide (OR 1.63 [1.37-1.94]) were associated with greater WL than FB. FB plus SGLT2i (OR 1.52 [1.19-1.94]) and FB plus acetazolamide (OR 1.81 [1.31-2.49]) were associated with WRF. FB plus thiazide was associated with both WRF (OR 1.78 [1.43-2.21]) and hypokalaemia (OR 1.69 [1.32-2.16]). Results were consistent in sensitivity analyses considering urine output, RCTs protocol-established furosemide doses, or daily furosemide dose. Congestion/decongestion scores and clinical outcomes were reported in around 50% of RCTs. In an underpowered exploratory analysis, mortality/rehospitalization was non-significantly lower with SGLT2i (OR 0.45 [0.19-1.07]).

Conclusions: FC and SNB improve surrogates of response to FB in AHF. SNB is also connoted by WRF and may induce hypokalaemia. The endpoints of diuretic RCTs should be revised and harmonized.