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

Abstract

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.

October 2023 at a glance: From prevention to diagnosis, prognosis and treatment of acute decompensation and comorbidities

“…No significant differences were observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints across different eGFR values at baseline. 18 EMPULSE showed the safety and beneficial effects of empagliflozin in patients hospitalized for acute HF further supporting the indication for an early start of sodium-glucose cotransporter 2 inhibitors after an acute HF event. [19][20][21] However, the impact of a concomitant use of mineralocorticoid receptor antagonists (MRAs) remains uncertain.…”

“…Patients with eGFR ≥60 ml/min/1.73 m 2 had greater weight loss compared to the others. No significant differences were observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints across different eGFR values at baseline 18 …”

Renal function and natriuresis‐guided diuretic therapy – a pre‐specified analysis from the PUSH‐AHF trial

“…This is consistent with recent findings on diuretic therapy in acute HF in both ADVOR with acetazolamide and CLOROTIC with thiazides. 18,19 In ADVOR, WRF occurred more frequently in patients randomized to acetazolamide versus placebo (40.5% vs. 18.9%, p = 0.009), while in CLOROTIC WRF occurred more often in patients randomized to hydrochlorothiazide (46.5% vs. 17.2%, p < 0.001). Putting these findings in perspective with our current analysis shows that with much higher doses of loop diuretics used in PUSH-AHF, the observed rate of WRF was increased with natriuresis-guided treatment, but as compared with SOC the difference was smaller than observed with acetazolamide or hydrochlorothiazide versus placebo.…”

Advances in Cardiorenal Medicine; the Year 2023 in Review

“…Historically, thiazides have been considered less potent with regard to provoking diuresis and natriuresis in patients with impaired kidney function [9,10]. However, a post hoc analysis of CLOROTIC revealed that the addition of eGFR-adjusted doses of oral hydrochlorothiazide could improve diuretic response across the eGFR spectrum, albeit with attenuated effect in patients with an eGFR <45 mL/min [11].…”