Decongestion in chronic heart failure (HF) is frequently complicated by renal dysfunction and diuretic resistance, limiting the effectiveness of conventional therapies. Investigators performed a prespecified post-hoc analysis of the DEA-HF randomized crossover trial to evaluate whether renal function and serum bicarbonate levels influence responses to different diuretic regimens in ambulatory patients with congestion-refractory HF. The results were published in the European Heart Journal Cardiovascular Pharmacotherapy.

The DEA-HF trial enrolled 42 patients who received three treatment strategies in random sequence: intravenous (IV) furosemide 250 mg alone, oral metolazone 5 mg plus IV furosemide 250 mg, and IV acetazolamide 500 mg plus IV furosemide 250 mg. The primary endpoint was 6-hour natriuresis, while secondary endpoints included 6-hour urine output and measures of clinical decongestion at 7±3 days.

Findings

• Patients with eGFR >30 mL/min/1.73 m² achieved significantly greater natriuresis and diuresis than those with eGFR ≤30 mL/min/1.73 m² (natriuresis: 4,735 mg vs 3,211 mg, p=0.0004; diuresis: 1.93 L vs 1.49 L, p=0.0078).
• In patients with eGFR >30 mL/min/1.73 m², metolazone plus furosemide produced greater natriuresis than acetazolamide plus furosemide (5,525 mg vs 4,379 mg, p=0.04).
• Metolazone plus furosemide also resulted in significantly higher natriuresis compared with furosemide monotherapy in patients with preserved renal function (5,525 mg vs 4,303 mg, p=0.014).
• Among patients with eGFR ≤30 mL/min/1.73 m², no significant differences in natriuresis were observed between metolazone, acetazolamide, or furosemide alone.
• Higher serum bicarbonate levels were independently associated with greater natriuretic and diuretic responses (4,858 mg vs 3,576 mg, p=0.0008; 1.99 L vs 1.56 L, p=0.0014).

The investigators concluded that renal function and serum bicarbonate levels may help identify patients most likely to benefit from intensified diuretic strategies. Metolazone appeared particularly effective in patients with eGFR >30 mL/min/1.73 m², whereas neither metolazone nor acetazolamide conferred additional benefit in patients with more advanced renal impairment.