Associations of comorbidities and co-medications with angioedema during the use of angiotensin converting enzyme-inhibitors within the United Kingdom clinical practice research Datalink

Abstract

Objectives: This study describes the occurrence of angioedema among patients initiating ACEI therapy and evaluates the association of this outcome with demographic factors, co-medication and chronic comorbidities. Methods: A nested case-control study was conducted in a cohort of patients newly treated with ACEIs from 2007 to 2014 in the CPRD. Cases who had angioedema only during ACEI treatment were identified using medical codes and were matched on the duration of ACEI treatment at the angioedema date (index date) with up to 20 controls who never had angioedema recorded. The use of co-medication (anti-diabetics, antihistamines, anti-asthmatics, non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, calcium channel blockers and statins), was acquired from CPRD prescription records within a three months' time window before the index date. The history of comorbidities (asthma, allergy, chronic obstructive pulmonary disease (COPD), diabetes mellitus and rheumatoid arthritis) was retrieved from medical records any time before the index date. Odds ratios (ORs) and p-values were estimated using univariate logistic regression analysis. Results: The cohort included 276,977 patients aged ≥ 45 years initiating ACEI therapy. The study population included 416 cases of angioedema during ACEI therapy matched with 4,335 controls. Age over 65 years was associated with angioedema. The proportions of asthma, allergy, COPD and rheumatoid arthritis were significantly higher in ACEI consumers who developed angioedema during ACEI therapy (ORs 1.83, 2.03, 2.08 and 2.83 respectively; p<0.001), compared to controls. History of diabetes and use of anti-diabetic drugs were associated with a decreased risk for angioedema (OR 0.73, P= 0.034). Antihistamines, anti-asthmatic drugs and systemic corticosteroids were associated with angioedema during ACEI therapy (ORs 25.64, 2.19 and 7.15 respectively; p<0.001). Conclusions: Angioedema during ACEI therapy was more frequent in patients over 65 years old and in patients with history of inflammatory comorbidities, such as asthma and allergies.