Objective: To explore an association between the use of β-adrenergic receptor agonists or antagonists and the onset of venous leg ulcers (VLUs). Design: Retrospective cohort study. Setting: Ambulatory setting of general practice in the United Kingdom. Patients: Patients followed by participating physicians. Main Outcome Measure: Onset of VLU. Results: A total of 414 887 patients registered in the General Practice Research Database met our study criteria for eligibility. Of these individuals, 62 886 were exposed to a β-adrenergic receptor agonist and 54 861 were exposed to a β-adrenergic receptor antagonist (6620 used both β-adrenergic receptor antagonists and agonists). Of those exposed to a β-adrenergic receptor agonist, 15.5% developed a VLU, whereas 18.4% of those who were not exposed developed a VLU. Of those exposed to a β-adrenergic receptor antagonist, 18.2% developed a VLU, whereas 19.9% of those not exposed developed a VLU. The odds ratio (OR) of association between β-adrenergic receptor antagonist and VLUs was 1.02 (95% confidence interval [CI], 0.99-1.04); for the association between β-adrenergic receptor agonist and VLUs, 0.84 (95% CI, 0.82-0.86). The fully adjusted ORs were 1.04 (95% CI, 0.98-1.11) and 0.44 (95% CI, 0.42-0.45), respectively. Furthermore, using propensity score models, we were able to confirm the association for β-adrenergic receptor agonist users. In addition, β-adrenergic receptor antagonist users in many of the propensity score quintiles were also protected from developing VLUs. Conclusions: A protective association between β-adrenergic receptor agonists and perhaps β-adrenergic receptor antagonists and VLUs exists. There is strong laboratory evidence to support these epidemiologic findings. The evidence in this study should not be used as a rationale for treatment of VLUs with β-adrenergic receptor agents but should be compelling for the consideration of a randomized clinical trial.
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