Pharmaco-epidemiological study of cardiorespiratory safety of β2-agonists for the treatment and management of asthma, chronic obstructive pulmonary disease (DOPD) and asthma-COPD overlap

Amegadzie, Joseph Emil (2021) Pharmaco-epidemiological study of cardiorespiratory safety of β2-agonists for the treatment and management of asthma, chronic obstructive pulmonary disease (DOPD) and asthma-COPD overlap. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Despite ample evidence underpinning the efficacy of β2-agonists in asthma and Chronic Obstructive Pulmonary Disease (COPD), the occurrence of β1-and β2- adrenoceptors in the heart suggests that β2-agonists may have deleterious cardiac effects. Therefore, patients who have asthma, COPD or both may be at increased risk of cardiorespiratory (CR) events because these diseases magnify the impact of these agents on the heart. In this thesis, I performed a systematic review and meta-analyses of the literature to provide a general overview of the comparative effectiveness and safety of inhaled medications. I conducted a retrospective cohort study to investigate gender differences in new-users of inhaled corticosteroids (ICS), short-or long-acting β2-agonist (SABA or LABA), ICS/LABA, short-or long-acting muscarinic antagonist (SAMA or LAMA) and a nested case-control study to test the association between β2-agonist-based medications and safety events for cardio-respiratory outcomes of major adverse cardiovascular events (MACE), all-cause mortality, and hospitalization for pneumonia using the United Kingdom Clinical Practice Research Datalink of patients with asthma, COPD or asthma- COPD overlap between 01-January-1998 and 31-July-2018. Results from the meta-analysis suggests that for patients with asthma–COPD overlap, LABA are associated with decreased risk of myocardial infarction in comparisons to non-LABA; and the combination therapy of ICS/LABA appears to reduce the risk of death or hospitalization in comparisons to placebo. Also, results from the gender-based analysis of pharmacotherapy use showed significant gender differences in new-users of inhaled pharmacotherapies among obstructive airways disease patients. In regards to the cardio-respiratory outcomes, new initiation of LABA, SABA or ICS/LABA compared to SAMA in COPD or SABA compared to ICS in asthma-COPD overlap was associated with an increased risk of MACE. However, among asthmatics, β2-agonists compared to ICS were not associated with risk of MACE. Consequently, starting LABA monotherapy or SABA monotherapy treatment was associated with an increased risk of all-cause mortality in patients with COPD. On the other hand, I observed no association with SABA, LABA or LABA/ICS in comparison with ICS or SAMA and the risk of pneumonia in patients with asthma, COPD or asthma-COPD overlap.

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