AUTHOR=Yeh Jun-Jun , Lai Mei-Chu , Yang Yu-Cih , Hsu Chung-Y. , Kao Chia-Hung 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.797623

DOI=10.3389/fcvm.2022.797623

ISSN=2297-055X

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 1118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analysed using Cox proportional regression; propensity scores were estimated using nonparsimonious 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.