Determinants of angiotensin converting enzyme-inhibitor (ACEI) intolerance and angioedema in the UK clinical practice research datalink

AIM: In this study we aimed to describe the occurrence and determinants of ACE-inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population.

METHODS: 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 = 4,335) on the duration of ACEI treatment. Switching to ARBs in the prescription records was used to identify ACEI intolerance cases (n = 24,709) which 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, co-morbidities and co-medication with AE and ACEI intolerance.

RESULTS: AE during ACEI therapy was associated with age over 65 years (OR 1.36, 95%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), anti-histamines (OR 21.25, 95%CI 16.44; 27.46) and systemic corticosteroids (OR 4.52, 95% CI: 3.26, 6.27). ACEI intolerance was significantly associated with more co-morbidities and co-medication compared to AE, including allergy (OR 2.02, 95% CI 1.96; 2.09), use of anti-asthmatic drugs (OR 1.51, 95% CI 1.42; 1.61) and anti-histamines (OR 1.53, 95% CI 1.43; 1.63).

CONCLUSIONS: Among ACEI users developing AE or ACEI intolerance several co-morbidities and co-medication classes were significantly more prevalent compared to ACEI users not developing these adverse reactions. This article is protected by copyright. All rights reserved.