Benzodiazepine use and mortality in chronic heart failure

Abstract

Introduction: The prognostic implications of using benzodiazepines (BZD) in heart failure (HF) patients are still unknown.

Objectives: This study aimed to assess the association of BZD use with all‑cause death in ambulatory, chronic HF patients.

Patients and methods: We investigated a retrospective cohort of ambulatory HF patients with left ventricular systolic dysfunction (LVSD). The patients were followed up from their first medical appointment until January 2021 and all‑cause mortality was the primary end point. The Cox regression analysis was used to assess the association between BZD use and all‑cause mortality. Subgroup analyses were performed considering age, sex, body mass index (BMI), respiratory disease, chronic kidney disease (CKD), and New York Heart Association (NYHA) class. Multivariable models were built to account for confounders.

Results: We studied 854 patients (69% men), of mean (SD) age 71 (13) years, of whom 51% had severe LSVD, and 242 (28.3%) regularly used BZD. During a median follow‑up of 46 months, 443 patients (51.9%) died. BZD use predicted no crude survival disadvantage in the entire investigated group and in the subgroup analysis according to sex, respiratory disease, BMI, and NYHA class. BZD use was not mortality‑associated among patients aged 75 years and younger. However, in those older than 75 years the hazard ratio (HR) of all‑cause death was 1.3 (95% CI, 0.99-1.69; P = 0.06). BZD use seemed safe in the patients without CKD, but in those with CKD it was associated with worse survival (HR, 1.33; 95% CI, 1.02-1.73). In a multivariable‑adjusted analysis, the use of BZD was independently associated with increased death risk (HR, 1.36; 95% CI, 1.06-1.75).

Conclusions: The patients medicated with BZD presented a 36% higher risk of dying. BZD should probably be used with caution, particularly in older HF patients and in those with CKD.