Intolerance to angiotensin converting enzyme inhibitors in asthma and the general population: a UK population-based cohort study

Background: Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs requiring switching to an angiotensin-II receptor blocker (ARB). ACEI intolerance may be mediated by bradykinin potentially affecting airway hyper-responsiveness.

Objective: Assess the risk of switching to ARBs in asthma.

Methods: We conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk of switching to ARBs in people with asthma, chronic obstructive pulmonary disease (COPD) and the general population were compared. Adjusted hazard ratios (HR) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.

Results: Of 642,336 new-users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR1.16, 95%CI 1.14-1.18, p=<0.001) and highest in those at BTS step ≥3 (HR1.35, 95%CI 1.32-1.39 and 1.18, 95%CI 1.15-1.22, p=<0.001 for patients aged ≥60 years and <60 years respectively). Hazard was highest with enalapril (HR1.25, 95%CI 1.18-1.34, p=<0.001; HR1.44, 95%CI 1.32-1.58, p=<0.001 for BTS step ≥3 asthma). No increased hazard was observed in COPD or those younger than 60 years at BTS step 1/2. The NNT varied by age, gender and BMI ranging between 21 and 4, being lowest in older women with BMI ≥25.

Conclusions: People with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The NNT varies by age, gender, BMI and BTS step. ARBs could potentially be considered first-line in people with asthma and in those with high-risk characteristics.