Daniel R Morales1, Cathy Jackson2, Brian J Lipworth3, Peter T Donnan4, Bruce Guthrie5. 1. Quality, Safety, and Informatics Group, Medical Research Institute, University of Dundee, Dundee. Electronic address: danielmorales@nhs.net. 2. Bute Medical School, University of St Andrews, Fife, Scotland. 3. Asthma and Allergy Research Group, Medical Research Institute, University of Dundee, Dundee. 4. Dundee Epidemiology and Biostatistics Unit, Medical Research Institute, University of Dundee, Dundee. 5. Quality, Safety, and Informatics Group, Medical Research Institute, University of Dundee, Dundee.
Abstract
BACKGROUND: β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy. METHODS: A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated. RESULTS: Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥20% in one in eight patients (P=.03), symptoms affecting one in 33 patients (P=.18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P=.02), one in 13 patients (P=.14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers. CONCLUSIONS: Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.
BACKGROUND: β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy. METHODS: A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated. RESULTS: Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥20% in one in eight patients (P=.03), symptoms affecting one in 33 patients (P=.18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P=.02), one in 13 patients (P=.14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers. CONCLUSIONS: Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.
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