Incidence And Risk Factors of Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Large Case-Control Study

Abstract

The incidence of ACEI-induced angioedema ranges from 0.1% to 0.7% affecting more women, African Americans, and adults over 65 years old. We sought to determine the incidence of ACEI-induced angioedema among different geographical regions of the U.S., comparing patients' characteristics and risk factors. A case-control study from 2008 to 2018 using electronic health records of an integrated health-care system across four states of the country. Cohort development software was used to obtain all ACEI prescriptions and angioedema was identified using ICD-CM codes 995.1 and T78.3 (Angioneurotic edema). Out of 145,101 patients who received an ACEI, 716 patients developed angioedema (0.49%; 95% CI, 0.46%-0.53%). Their median age was 66 years (Range: 21.0, 99.0), 50.4% were female, 88.5% Caucasian, and 84.8% of the cases were prescribed lisinopril. The risk of ACEI-induced angioedema was higher among women compared to men (OR 1.44; 95% CI; 1.24-1.67; P < .001), African American compared to Caucasian (OR 2.88; 95% CI; 2.14-3.89; P <.001), patients with concomitant use of NSAIDs compared to patients not on NSAIDs (OR 2.28; 95% CI; 1.85-2.8; P <.001), and in the upper Midwest compared to the Southeast (OR 1.57; 95% CI; 1.24-1.99; P < .001). Seventy-nine patients (11%) had ACEI-induced angioedema within one month of being prescribed an ACEI, and 244 (34%) during the first year. The incidence and risk factors for ACEI-induced angioedema in our cohort were similar to previous reports. Women, African Americans, patients on NSAIDs, and patients in the upper Midwest were at higher risk of ACEI-induced angioedema.