title: An assessment of the association between carvedilol exposure and severe hypersensitivity reactions, angioedema, and anaphylactic reactions: a retrospective nested case-control analysis.
abstract: BACKGROUND
  There 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: GlaxoSmithKline, 1250 S. Collegeville Road,Collegeville, PA 19426, USA. carol.e.koro@gsk.com
authors.forename: Carol E
authors.initials: CE
authors.lastname: Koro
authors.forename: Margaret D
authors.initials: MD
authors.lastname: Sowell
authors.forename: Monika
authors.initials: M
authors.lastname: Stender
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects*; D000077261:Carvedilol; D016022:Case-Control Studies; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol