Supplementary Material for: Documented adverse drug reactions and discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease

Background: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation. Methods: In this retrospective cohort of U.S. veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented ADRs with treatment discontinuation. Results: There were 882,441 (73.0%) individuals in the current user group and 326,794 (27.0%) in the discontinued group. There were 26,434 documented ADRs, with at least one documented ADR in 7,520 (0.9%) current users and 9,569 (2.9%) of the discontinued group. ADR presence was associated with treatment discontinuation, aOR 4.16 (95% CI 4.03, 4.29). The most common documented ADRs were cough (37.3%), angioedema (14.2%), and allergic reaction (10.4%). ADRs related to angioedema (aOR 3.81, 95% CI 3.47, 4.17), hyperkalemia (aOR 2.03, 95% CI 1.84, 2.24), peripheral edema (aOR 1.53, 95% CI 1.33, 1.77), or acute kidney injury (aOR 1.32, 95% CI 1.15, 1.51) were associated with treatment discontinuation. Conclusions: ADRs leading to drug discontinuation were infrequently documented. ADR types were differentially associated with treatment discontinuation. An understanding of which ADRs lead to treatment discontinuation provides an opportunity to address them at a healthcare system level.