Z-drugs are associated with cardiovascular outcomes among patients with heart failure: a population-based cohort study in Hong Kong

Abstract

Aims: Patients with heart failure (HF) often suffered from concomitant insomnia. Non-benzodiazepine GABA receptor agonists (Z-drugs) are hypnotics commonly used for treating insomnia. The effect of Z-drugs on the outcomes of patients with HF is nonetheless sparse. Our study aims to investigate the association of Z-drugs and the risks of adverse cardiovascular outcomes in the HF population.

Methods and results: A total of 202 585 patients (mean age 73.24, 47.8% male) diagnosed with HF between 2001 and 2020 were identified from Hong Kong Clinical Data Analysis Reporting System. Propensity score matching and competing risk regression with Cox proportional hazard models were performed to evaluate the use of Z-drugs (n = 14 765, 7.3%) and the risks of primary composite endpoint of HF rehospitalization and cardiovascular death (CVD), HF rehospitalization, CVD, and all-cause mortality. Over a median follow-up of 10.5 years (interquartile range 5.7-15.8 years), use of Z-drugs was correlated with 21% higher risk of primary composite endpoint [multivariable adjusted sub-distribution hazard ratio (SHR): 1.21, 95% confidence interval (CI): 1.18-1.24], 21% higher risk of HF rehospitalization (SHR: 1.21, 95% CI: 1.17-1.24), 11% higher risk of CVD (SHR: 1.11, 95% CI: 1.07-1.15), and 15% higher risk of all-cause mortality (HR: 1.15, 95% CI: 1.11-1.18). A duration-dependent relationship was also observed, with worse outcomes seen in long-term use compared with short-term use.

Conclusion: Our findings suggest that the use of Z-drugs increases the risks of adverse cardiovascular outcomes among patients with HF.

Keywords: Cardiovascular death; Heart failure; Hypnotics; Insomnia; Z-drugs.