Sex differences in clinical characteristics and outcomes in the CLOROTIC (combining loop with thiazide diuretics for decompensated heart failure) trial

Abstract

Aims: The addition of hydrochlorothiazide (HCTZ) to furosemide improved the diuretic response in patients with acute heart failure (AHF) in the CLOROTIC trial. Our aim was to evaluate if there were differences in clinical characteristics and outcomes according to sex.

Methods: This is a post-hoc analysis of the CLOROTIC trial, including 230 patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The primary and secondary outcomes included changes in weight and patient-reported dyspnoea 72 and 96 h after randomization, metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. The influence of sex on primary, secondary and safety outcomes was evaluated.

Results: One hundred and eleven (48%) women were included in the study. Women were older and had higher values of left ventricular ejection fraction. Men had more ischemic cardiomyopathy and chronic obstructive pulmonary disease and higher values of natriuretic peptides. The addition of HCTZ to furosemide was associated to a greatest weight loss at 72/96 h, better metrics of diuretic response and higher 24-h diuresis compared to placebo without significant differences according to sex (all p-values for interaction were not significant). Worsening renal function occurred more frequently in women (OR [95%CI]: 8.68 [3.41-24.63]) than men (OR [95%CI]: 2.5 [0.99-4.87]), p = 0.027. There were no differences in mortality or rehospitalizations at 30/90 days.

Conclusion: Adding HCTZ to intravenous furosemide is an effective strategy to improve diuretic response in AHF with no difference according to sex, but worsening renal function was more frequent in women.

Clinical trial registration: Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36.

Keywords: Deterioro de función renal; Diuretics; Diuréticos; Heart failure; Insuficiencia cardiaca; Sex; Sexo; Thiazides; Tiazidas; Worsening renal function.