Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post‐hoc analysis of the CLOROTIC trial

Aims In 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 results This 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 m 2 (range 14–109) and 23% had eGFR ≥60 ml/min/1.73 m 2 (group 1), 24% from 45 to 59 ml/min/1.73 m 2 (group 2), and 53% <45 ml/min/1.73 m 2 (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 rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p ‐values for interaction were no significant). Conclusion The addition of eGFR‐adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum. Clinical Trial Registration: ClinicalTrials.gov : NCT01647932; EudraCT number: 2013–001852‐36.