An Assessment of the Association Between Carvedilol Exposure and Severe Hypersensitivity Reactions, Angioedema, and Anaphylactic Reactions: A Retrospective Nested Case–Control Analysis

BackgroundThere is limited information in the literature regarding the risk of severe hypersensitivity reactions due to different β-blocking agents. Most of the available information addresses the potential for increased severity of anaphylaxis or poor response to treatments among patients receiving β-blocking agents.ObjectiveThe objective of this study was to estimate the incidence rates of severe hypersensitivity reactions (angioedema and anaphylactic reactions) for various β-blockers and to examine the risk of severe hypersensitivity reactions in patients exposed to carvedilol extended-release compared with carvedilol and compared with other β-blockers.MethodsA case–control analysis nested within a cohort of β-blocker users in the LabRx Database was conducted. A case was defined as an incident hypersensitivity reaction of either anaphylactic shock (International Classification of Diseases, 9th Revision [ICD-9] code 995.0) or angioneurotic edema (ICD-9 code 995.1). Three controls were matched to each case. Patients were classified according to their β-blocker exposure in the 30 day-period before the index date. Conditional logistic regression was used to calculate odds ratios and 95% CIs.ResultsA total of 1,810,487 β-blocker users were identified; 7811 hypersensitivity cases and 23,433 controls were included in this analysis. The mean (SD) age of the cohort was 53 (14) years, and 49% were men. The overall incidence rates of severe hypersensitivity reactions among various β-blockers categories were similar to that in the overall β-blocker users cohort (2.40 per 1000 person-years [95% CI, 2.35–2.45]). The odds ratios of severe hypersensitivity reaction for carvedilol extended-release compared with carvedilol and with other long-acting β-blockers were 0.86 (95% CI, 0.48–1.53) and 1.10 (95% CI, 0.90–1.35), respectively.ConclusionsThis retrospective database analysis of mostly middle-aged patients detected no statistically significant differences in the likelihood of severe hypersensitivity reactions among patients who received carvedilol extended-release versus carvedilol or other long-acting β-blockers.