Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea: a population-based cohort study in target trial emulation framework

Anthony Chen; Chengsheng Ju; Isla S Mackenzie; Thomas M MacDonald; Allan D Struthers; Li Wei; Kenneth K C Man

doi:10.1016/j.lanepe.2023.100715

Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea: a population-based cohort study in target trial emulation framework

Lancet Reg Health Eur. 2023 Aug 4:33:100715. doi: 10.1016/j.lanepe.2023.100715. eCollection 2023 Oct.

Authors

Anthony Chen^{1

2}, Chengsheng Ju¹, Isla S Mackenzie³, Thomas M MacDonald³, Allan D Struthers³, Li Wei^{1

4

5}, Kenneth K C Man^{1

4

5

6}

Affiliations

¹ Research Department of Practice and Policy, UCL School of Pharmacy, Mezzanine Floor, BMA House, Tavistock Square, London, WC1H 9JP, England.
² Faculty of Medicine & Health Sciences, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, England.
³ Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland.
⁴ Laboratory of Data Discovery for Health (D4H), Hong Kong Science Park, Hong Kong, China.
⁵ Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, England.
⁶ Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Abstract

Background: There is no real-world evidence regarding the association between beta-blocker use and mortality or cardiovascular outcomes in patients with obstructive sleep apnoea (OSA). We aimed to investigate the impact of beta-blocker use on all-cause mortality and cardiovascular diseases (CVDs) in patients with OSA.

Methods: We conducted a target trial emulation study of 37,581 patients with newly diagnosed OSA from 1st January 2000 to 30th November 2021 using the IMRD-UK database (formerly known as the THIN database). We compared the treatment strategies of initiating beta-blocker treatment within one year versus non-beta-blocker treatment through the method of clone-censor-weight. Covariates, including patients' demographics, lifestyle, comorbidities, and recent medications, were measured and controlled. Patients were followed up for all-cause mortality or composite CVD outcomes (angina, myocardial infarction, stroke/transient ischaemic attack, heart failure, or atrial fibrillation). We estimated the five-year absolute risks, risk differences and risk ratio with 95% confidence intervals (CIs) with standardised, weighted pooled logistic regression, which is a discrete-time hazard model for survival analysis. Several sensitivity analyses were performed, including multiple imputation addressing the missing data.

Findings: The median follow-up time was 4.1 (interquartile range, 1.9-7.8) years. The five-year absolute risk of all-cause mortality and CVD outcomes were 4.9% (95% CI, 3.8-6.0) and 13.0% (95% CI, 11.4-15.0) among beta-blocker users, and 4.0% (95% CI, 3.8-4.2) and 9.4% (95% CI, 9.1-9.7) among non-beta-blocker users, respectively. The five-year absolute risk difference and risk ratio between the two groups for all-cause mortality and CVD outcomes were 0.9% (95% CI, -0.2 to 2.1) and 1.22 (95% CI, 0.96-1.54), and 3.5% (95% CI, 2.1-5.5) and 1.37 (95% CI, 1.22-1.62), respectively. Findings were consistent across the sensitivity analyses.

Interpretation: Beta-blocker treatment was associated with an increased risk of CVD and a trend for an increased risk of mortality among patients with OSA. Further studies are needed to confirm our findings.

Funding: Innovation and Technology Commission of the Hong Kong Special Administration Region Government.

Keywords: Beta-blocker; Cohort study; Obstructive sleep apnoea; Trial emulation.