Association between the use of beta-adrenergic receptor agents and the development of venous leg ulcers

To explore an association between the use of beta-adrenergic receptor agonists or antagonists and the onset of venous leg ulcers (VLUs).

Retrospective cohort study.

Ambulatory setting of general practice in the United Kingdom. Patients Patients followed by participating physicians.

Onset of VLU.

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 beta-adrenergic receptor agonist and 54 861 were exposed to a beta-adrenergic receptor antagonist (6620 used both beta-adrenergic receptor antagonists and agonists). Of those exposed to a beta-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 beta-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 beta-adrenergic receptor antagonist and VLUs was 1.02 (95% confidence interval [CI], 0.99-1.04); for the association between beta-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 beta-adrenergic receptor agonist users. In addition, beta-adrenergic receptor antagonist users in many of the propensity score quintiles were also protected from developing VLUs.

A protective association between beta-adrenergic receptor agonists and perhaps beta-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 beta-adrenergic receptor agents but should be compelling for the consideration of a randomized clinical trial.