Discontinuation of RAS Inhibition After an Acute Decline in Estimated Glomerular Filtration Rate

Importance Although renin-angiotensin system inhibitors (RASIs) slow the progression of chronic kidney disease, these agents are frequently discontinued if acute declines in the estimated glomerular filtration rate (eGFR) occur after their initiation. Objective To examine the risk for cardiovascular, kidney, and mortality outcomes associated with discontinuation vs continuation of RASIs in patients with an acute decline in eGFR after RASI initiation. Design, Setting, and Participants This retrospective cohort study using a target trial emulation approach leveraged electronic health record data from the Manitoba Centre for Health Policy that were linked to vital statistics in the province of Manitoba, Canada. Propensity score matching was applied to identify adults (aged ≥18 years) receiving new prescriptions for RASIs between January 1, 2008, and December 31, 2021, who subsequently had an eGFR decline of more than 15% within 90 days of the prescription. Data were analyzed between January 14, 2024, and January 22, 2026. Exposure RASI discontinuation (vs continuation) defined based on whether a RASI prescription was refilled within 90 days after a decline in eGFR of 15% had occurred. Main Outcomes and Measures The primary outcomes of end-stage kidney disease (ESKD) or death, and secondary outcomes of major adverse cardiovascular events (MACEs) (including myocardial infarction, heart failure, stroke, or cardiovascular mortality) or acute kidney injury (AKI) were examined after 180 days. Cox proportional hazards models were used to compare the exposure with the outcomes in an intention-to-treat approach. Results A total of 4233 patients (mean SD age, 64.6 16.2 years; 2697 male 51.1%) who had a more than 15% decline in eGFR after starting a RASI were included; 1411 patients (33.3%) discontinued RASIs, and 2822 (66.6%) continued RASIs . Patients who discontinued vs continued RASIs had a higher risk of death (hazard ratio HR, 1.23; 95% CI, 1.07-1.41) and ESKD (HR, 1.74; 95% CI, 1.28-2.38). Their risk of MACEs (HR, 1.13; 95% CI, 0.99-1.28) and AKI (HR, 1.11; 95% CI, 0.90-1.37) was not significantly higher. Conclusions and Relevance This cohort study found that discontinuation of RASIs after an acute decline in eGFR was associated with ESKD and death compared with continuing RASIs. These findings suggest that further study is needed to understand reasons for frequent discontinuation of RASIs and devise strategies to improve their persistent use.