The safety of cardioselective β₁-blockers in asthma: literature review and search of global pharmacovigilance safety reports

Abstract

Beta-blockers are key in the management of cardiovascular diseases, but blocking airway beta2-receptors can cause severe and sometimes fatal bronchoconstriction in people with asthma. Although cardio-selective beta1-blockers may be safer than non-selective beta-blockers, they remain relatively contraindicated and under-prescribed. We review the evidence of the risk associated with cardio-selective beta1-blocker use in asthma.MethodsWe searched “asthma” AND “beta-blocker” in PubMed and EmbaseOvid from start to May 2020. The World Health Organisation global database of individual case safety reports (VigiBase) was searched for reports of fatal asthma or bronchospasm and listed cardio-selective beta1-blockers use (accessed February 2020). Reports were examined for evidence of pre-existing asthma.ResultsPubMed and EmbaseOvid searches identified 304 and 327 publications respectively. No published reports of severe or fatal asthma associated with cardio-selective beta1-blockers were found. Three large observational studies reported no increase in asthma exacerbations with cardio-selective beta1-blocker treatment. The VigiBase search identified five reports of fatalities in patients with pre-existing asthma and reporting asthma or bronchospasm during cardio-selective beta1-blocker use. Four of these deaths were unrelated to cardio-selective beta1-blocker use. The circumstances of the fifth death were unclear.ConclusionsThere were no published reports of cardio-selective beta1-blockers causing asthma death. Observational data suggest that cardio-selective beta1-blocker use is not associated with increased asthma exacerbations. We found only one report of an asthma death potentially caused by cardio-selective beta1-blockers in a patient with asthma in a search of VigiBase. The reluctance to use cardio-selective beta1-blockers in people with asthma is not supported by this evidence.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…Among RAS blockers, ARBs should be preferred because of the risk of developing cough during treatment with ACEis, which may be particularly disturbing in asthmatic patients. It is recommended to avoid BBs for antihypertensive treatment in patients with asthma because the safety margin of these drugs is smaller than in chronic COPD, where BBs are safe [1509], although this is a controversial issue [1510]. Nevertheless, a cautious use of BBs in patients with compelling indications to balance individual benefits and risks appears reasonable.…”

Cardiovascular diseases or type 2 diabetes mellitus and chronic airway diseases: mutual pharmacological interferences

“…No cases of cardioselective β 1 -blockers causing asthma mortality have been reported. 76 β-AR blockers may induce a reduction in lung function during the early part of the treatment period, which is modest, does not persist, and does not predict exacerbations in COPD patients, 77 and increased mortality in patients with severe COPD. 78 ACE inhibitors and AT1 receptor antagonists.…”

Carbazole and Simplified Derivatives: Novel Tools toward β-Adrenergic Receptors Targeting

“…In particular, the stimulation of β1-ARs, that in turn increases intracellular levels of cyclic-AMP and consequently of Ca 2+ , may account for the activation of the cardiac hypertrophic pathway [14,15]. In this view, the possibility to design and develop even more selective β1-ARs blockers still represents an important goal for cardiovascular translational research and an open field to be investigated [16][17][18][19][20].…”