Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

Abstract

Aim: 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.

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 = 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.

Results: 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).

Conclusions: 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.

Keywords: ACE inhibitor intolerance; ACE inhibitors; angioedema; angiotensin II receptor blockers; case-control studies; drug-related side effects and adverse reactions.

Figure 1

Time to the development of angiotensin‐converting enzyme inhibitor (ACEI) intolerance and angioedema during ACEI therapy. (A) Kaplan ‐Meier curves for time to the development of AE during ACEI therapy. Kaplan‐Meier curves were constructed for cases only. The top left rectangle indicates the area of Kaplan‐Meier curve depicted in the bottom right panel. The bottom right panel shows time to event during the first year of follow‐up. (B) Kaplan ‐Meier curves for time to switching to ARBs. Kaplan‐Meier curves were constructed for cases only. The top left rectangle indicates the area of Kaplan‐Meier curve depicted in the bottom right panel. The bottom right panel shows time to event within the first year of follow‐up. AE, angioedema; ARB, angiotensin II receptor blocker