title: Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.
abstract: The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population.
  
  
  
  Two nested case-control studies were conducted in a cohort of 276 977 patients aged ≥45 years initiating ACEIs from 2007 to 2014 in the UK Clinical Practice Research Datalink (CPRD). Cases of AE occurring for the first time during ACEI therapy (n = 416) were matched with AE-free controls (n = 4335) on the duration of ACEI treatment. Documented switches to angiotensin-II receptor blockers in the prescription records were used to identify ACEI-intolerance cases (n = 24 709), and these were matched with continuous ACEI users (n = 84 238) on the duration of ACEI therapy. Conditional logistic regression was used to assess the associations of demographic factors, comorbidities and comedication with AE and ACEI intolerance.
  
  
  
  AE during ACEI therapy was associated with age over 65 years [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.07, 1.73], history of allergy (OR 1.53, 95% CI 1.19, 1.96), use of calcium channel blockers (OR 1.57, 95% CI 1.23; 2.01), use of antihistamines (OR 21.25, 95% CI 16.44, 27.46) and use of systemic corticosteroids (OR 4.52, 95% CI 3.26, 6.27). ACEI intolerance was significantly associated with more comorbidities and comedication compared with AE, including allergy (OR 2.02, 95% CI 1.96, 2.09), use of antiasthmatic drugs (OR 1.51, 95% CI 1.42, 1.61) and use of antihistamines (OR 1.53, 95% CI 1.43, 1.63).
  
  
  
  Among ACEI users developing AE or ACEI intolerance, several comorbidities and comedication classes were significantly more prevalent compared with ACEI users not developing these adverse reactions.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Seyed Hamidreza
authors.initials: SH
authors.lastname: Mahmoudpour
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ekaterina Vitalievna
authors.initials: EV
authors.lastname: Baranova
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Souverein
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands.|Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.|Institute of Cardiovascular Science, faculty of Population Health Sciences, University College London, London, UK.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anke Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000453:epidemiology*; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015995:Prevalence; D012307:Risk Factors; D012737:Sex Factors; D006113:United Kingdom
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents
keywords: ACE inhibitor intolerance; ACE inhibitors; angioedema; angiotensin II receptor blockers; case-control studies; drug-related side effects and adverse reactions