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

TY - JOUR

T1 - Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea

T2 - a population-based cohort study in target trial emulation framework

AU - Chen, Anthony

AU - Ju, Chengsheng

AU - Mackenzie, Isla S.

AU - MacDonald, Thomas M.

AU - Struthers, Allan D.

AU - Wei, Li

AU - Man, Kenneth K.C.

N1 - Funding Information: Innovation and Technology Commission of the Hong Kong Special Administration Region Government.This work was partially supported by grant ITC RC/IHK/4/7 from the Hong Kong Special Administrative Region Goverment. We would like to thank Dr. Edouard L. Fu from Brigham and Women's Hospital and Harvard Medical School for comments on an earlier version of this manuscript. Copyright: © 2023 The Author(s).

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - Beta-blocker

KW - Cohort study

KW - Obstructive sleep apnoea

KW - Trial emulation

UR - https://www.scopus.com/pages/publications/85167440473

U2 - 10.1016/j.lanepe.2023.100715

DO - 10.1016/j.lanepe.2023.100715

M3 - Article

C2 - 37601338

AN - SCOPUS:85167440473

SN - 2666-7762

VL - 33

JO - The Lancet Regional Health - Europe

JF - The Lancet Regional Health - Europe

M1 - 100715

ER -