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

Abstract

ObjectiveWe investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).MethodsBCAS 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)}.ResultsCompared 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.ConclusionThe 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.