Relationships Between Bronchodilators, Steroids, Antiarrhythmic Drugs, Antidepressants, and Benzodiazepines and Heart Disease and Ischemic Stroke in Patients With Predominant Bronchiectasis and Asthma

Jun-Jun Yeh; Mei-Chu Lai; Yu-Cih Yang; Chung-Y Hsu; Chia-Hung Kao

doi:10.3389/fcvm.2022.797623

Relationships Between Bronchodilators, Steroids, Antiarrhythmic Drugs, Antidepressants, and Benzodiazepines and Heart Disease and Ischemic Stroke in Patients With Predominant Bronchiectasis and Asthma

Front Cardiovasc Med. 2022 Feb 17:9:797623. doi: 10.3389/fcvm.2022.797623. eCollection 2022.

Authors

Jun-Jun Yeh^{1

2}, Mei-Chu Lai³, Yu-Cih Yang^{2

4}, Chung-Y Hsu⁵, Chia-Hung Kao^{5

6

7

8}

Affiliations

¹ Department of Family Medicine, Chest Medicine, Geriatric Medicine and Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
² College of Medicine, China Medical University, Taichung, Taiwan.
³ Department of Laboratory Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
⁴ Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
⁵ Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.
⁶ Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung, Taiwan.
⁷ Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
⁸ Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.

Abstract

Objective: We investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).

Methods: BCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting β2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}.

Results: Compared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25-4.33), 2.65 (1.87-3.75), 2.66 (1.74-4.05), 2.53 (1.61-3.99), 1.76 (1.43-2.18), 9.88 (3.27-30.5), and 1.73 (1.15-2.58), respectively except fludiazepam 1.33 (0.73-2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs <415, ICSs ≤ 30 days were 1.10 (0.38-3.15), 2.95 (0.22-38.8), 1.45 (0.76-2.77). The aHRs (95% CIs) for current and recent alprazolam were 1.78 (1.09-2.93) and 777.8 (1.34-451590.0); for current and past fludiazepam were 1.39 (0.75-2.59) and 1.29 (0.42-4.01) and for past alprazolam was 1.57 (0.55-4.46); respectively. The aHRs (95% CIs) for alprazolam >30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78-3.29), 2.43 (0.90-6.55), 5.02 (1.76-14.3), and 2.28 (1.43-3.62), respectively.

Conclusion: The bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.

Keywords: NHIRD; National Health Insurance Research Database; bronchiectasis-asthma combination; heart disease; ischemic stroke; medicine.