Table 2. BfArM’s ADR-database analysis: Characteristics of validated ACEi angioedema cases and validated ACEi controls.
| BfArM’s ADR-database analysis | characteristics of validated ACEi angioedema cases and validated controls | validated ACEi angioedema cases versus validated ACEi controls | ||||
|---|---|---|---|---|---|---|
| validated ACEi angioedema cases (n = 121) | validated ACEi controls (n = 242) | unadjusted OR [+/- 95% CI] | logistic regression OR [+/- 95% CI] | logistic regression p-values | logistic regression + imputation (MICE) p-values | |
| completeness score a | 0.74 [0.65–0.82] | 0.71 [0.65–0.77] | - | - | - | - |
| patient demographics b | ||||||
| mean age (median) | 64.5 (68) | 63.5 (65) | - | 1.5 [0.9–2.7]´ | 0.121 | 0.099 |
| [years] | - | |||||
| female | 46.3% (56) | 55.8% (135) | 0.7 [0.4–1.0] | 0.9 [0.5–1.5] | 0.569 | 0.665 |
| male | 53.7% (65) | % (105) | ||||
| smoking and drinking | ||||||
| habits, allergic | ||||||
| conditions | ||||||
| smoker c | 14.0% (17) | 3.3% (8) | 4.8 [2.0–11.4]* | 2.7 [1.0–7.6] | 0.058 | 0.043* |
| alcohol consumption d | 9.1% (11) | 2.5% (6) | 3.9 [1.4–10.9]* | 2.9 [0.8–10.4] | 0.098 | 0.088 |
| allergy e | 12.4% (15) | 10.3% (25) | 1.2 [0.6–2.4] | 1.0 [0.5–2.3] | 0.942 | 0.988 |
| angioedema f | 24.0% (29) | - | - | - | - | - |
| comorbidities g | ||||||
| renal disorders | 9.9% (12) | 8.7% (21) | 1.2 [0.5–2.4] | 1.0 [0.4–2.3] | 0.953 | 0.749 |
| diabetes | 15.7% (19) | 13.2% (32) | 1.2 [0.7–2.3] | 1.1 [0.5–2.2] | 0.892 | 0.951 |
| asthma/COPD | 9.1% (11) | 6.2% (15) | 1.5 [0.7–3.4] | 1.8 [0.7–4.8] | 0.253 | 0.231 |
| administered ACEi h | ||||||
| ramipril | 67.8% (82) | 75.2% (182) | 0.7 [0.4–1.1] | 1.4 [0.4–5.0] | 0.620 | 0.997 |
| enalapril | 16.5% (20) | 12.4% (30) | 1.4 [0.8–2.6] | 1.4 [0.4–5.8] | 0.607 | 0.822 |
| lisinopril | 10.7% (13) | 9.1% (22) | 1.2 [0.6–2.5] | 1.5 [0.4–6.7] | 0.563 | 0.770 |
| comedication i | ||||||
| β-Blocker | 28.1% (34) | 23.1% (56) | 1.3 [0.8–2.1] | 1.6 [0.8–3.0] | 0.165 | 0.275 |
| diuretics | 13.2% (16) | 17.4% (42) | 0.7 [0.4–1.4] | 0.4 [0.2–0.8]* | 0.023* | 0.023* |
| calcium antagonists | 17.4% (21) | 9.1% (22) | 2.1 [1.1–4.0]* | 1.6 [0.7–3.3] | 0.248 | 0.181 |
| NSAID | 21.5% (26) | 19.8% (48) | 1.1 [0.6–1.9] | 0.5 [0.3–1.0] | 0.057 | 0.083 |
| everolimus | 5.8% (7) | 0.0% (0) | - | - | - | - |
| alteplase | 0.8% (1) | 0.0% (0) | - | - | - | - |
| seriousness criteria j | ||||||
| serious | 89.3% (108) | 53.7% (130) | 7.2 [3.8–13.4]* | 7.7 [3.9–15.1]* | < 0.001* | < 0.001* |
| death | 3.3% (4) | 1.2% (3) | 2.7 [0.6–12.4] | - | - | - |
| life-threatening | 28.9% (35) | 5.0% (12) | 2.8 [1.6–4.8]* | - | - | - |
| hospitalization | 49.6% (60) | 28.5% (69) | 2.5 [1.6–3.9]* | - | - | - |
| disabling | 0.8% (1) | 5.0% (12) | 0.2 [0.0–1.2] | - | - | - |
*OR = 1 is not included; OR > 1 reported more often in validated ACEi angioedema cases; OR < 1 reported more often in validated ACEi controls
a in cases and controls, most data referring to the variable "time to onset" was incomplete or missing. The calculation of the completeness score is described in the Methods section: 2.2.3. BfArM’s ADR-database: documentation quality of validated cases.
b validated ACEi angioedema cases: age unknown in 21 reports, gender unknown in 2 reports.
c refers to current smoking at the time of the reported ADR. Former smokers were classified as non-smokers.
d information about the amount of alcohol consumed (daily/weekly) was rare and may not have been reported. It was not possible to classify the cases in patients with a high or moderate alcohol consumption due to inaccurate information. Therefore, all cases in which any alcohol consumption was reported were counted, independent of the amount.
e the term "allergy" refers to a reported allergy and the occurrence of any allergic and hypersensitivity reactions reported in the history of the patient.
f the term "angioedema" summarizes previous angioedema or swellings coded in the SMQ "angioedema (narrow)" reported in the history of the patient.
g refers to renal disorders, diabetes, asthma/COPD (chronic obstructive pulmonary disease) reported in the patients’ history or as a drug indication term for the used comedication.
h the three ACEi monosubstances most frequently reported as "suspected/interacting" are tabulated. The remaining ACEi (not listed) were reported fewer than 5 times.
i the analysis of the most frequently reported and most relevant comedications is based on monosubstances and combination products of the tabulated drug substances and/or drug classes and corresponds to the ATC classification. All drugs co-reported to the "suspected/interacting" ACEi were counted as "concomitant", regardless of whether they were reported as "suspected", "interacting" or "concomitant".
j One ADR report may yield information about more than one seriousness criterion, therefore, the number of reported seriousness criteria exceeds that of the ADR reports.