Aims To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF). Methods and results A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48% women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [−2.3 vs. −1.5 kg; adjusted estimated difference (notionally 95% confidence interval) −1.14 (−1.84 to −0.42); P = 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P = 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P = 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P < 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine >26.5 μmoL/L or decrease in eGFR >50%; 46.5 vs. 17.2%; P < 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations. Conclusion The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF.

AimsIn patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum.Methods and ResultsThis post‐hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43 mL/min/1.73 m2 (range 14‐109) and 23% had eGFR >60 mL/min/1.73 m2 (group 1), 24% from 45 to 59 mL/min/1.73 m2 (group 2), and 53% <45 mL/min/1.73 m2 (group 3). Patients treated with HCTZ had greatest weight loss at 72 h in all three groups, but patients in group 1 had a significantly greater response (−2.1 kg [−3.0 to 0.5]), compared to patients in groups 2 (−1.3 kg [−2.3 to 0.2]) and 3 (−0.1 kg [−1.3 to 0.4]) (p value for interaction = 0.246). At 96 h, the differences in weight were − 1.8 kg [−3.0 to −0.3], −1.4 kg [−2.6 to 0.3], and − 0.5 kg [−1.3 to −0.1] in groups 1, 2, and 3, respectively (p value for interaction = 0.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalisations, or safety endpoints (impaired renal function, hyponatremia, and hypokalaemia) among the three eGFR groups (all p‐values for interaction were no significant).ConclusionThe addition of eGFR‐adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum.This article is protected by copyright. All rights reserved.

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