Effect of Cessation of Renin-Angiotensin System Inhibitors on Clinical Outcomes in AKI

Background: In the ELAIA-2 trial, we investigated whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves clinical outcomes in patients with AKI. One of the findings of the ELAIA-2 trial was that the proportion of RAASi prescribed were significantly altered due to the best practice alerts the providers received. We conducted a subgroup analysis to evaluate the differences in clinical outcomes between patients with RAASi inhibitors discontinued vs. cessation and clinical outcomes using an instrumental variable regression. A secondary objective was to evaluate the existence of a causal relationship between ACE/ARB inhibition and clinical outcomes and to evaluate if the effect of the drugs is influenced by potential patient characteristics using an instrumental variable regression. Methods: All statistical analysis was conducted on STATA (Stata, v.18., College Station, TX). Results: There was a significantly higher proportion of in-patient mortality, dialysis, AKI progression and composite outcomes at 14-days follow-up in the group that had their ACE/ARB discontinued. However, we observed no causal relationship of cessation of RAASi on clinical outcomes upon instrumental variable regression. This was the case amongst all examined subgroups including congestive heart failure, chronic kidney disease, pulmonary disease, hypertension, depression, malignancy and liver disease (Table 1). Conclusion: There is minimal causal relationship between RAASi cessation and outcomes among hospitalized patients with AKI. Table 1: Regression of RAASi on Clinical Outcomes - Composite Outcome AKI Progression Mortality Dialysis Unadjusted Cohort 2.49 (1.96-3.16) 2.08 (1.62-2.67) 4.88 (3.24-7.33) 4.34 (2.31-8.16) Instrumental Variable Regression CHF Absent 0.153 (-0.34-0.65) 0.214 (-0.251-0.679) 0.0532 (-0.32-0.43) 0.144 (-0.0115-0.403) CHF Present -0.17 (-0.61-0.27) -0.088 (-0.486-0.309) -0.042 (-0.36-0.276) 0.037 (-0.0155-0.23) CKD Absent 0.297 (-0.22-0.82) 0.251 (-0.237-0.738) 0.245 (-0.146-0.636) 0.137 (-0.121-0.395) HTN Absent 0.469 (-0.454-1.39) 0.398 (-0.458-1.25) 0.323 (-0.378-1.02) 0.38 (-0.206-0.965) HTN Present -0.103 (-0.462-0.256) 0.0000938 (-0.33-0.33) -0.061 (-0.33-0.207) 0.0266 (-0.139-0.192) Liver Disease Absent -0.054 (-0.41-0.3) 0.048 (-0.274-0.37) 0.048 (-0.274-0.37) 0.082 (-0.087-0.251) Liver Disease Present 0.503 (-0.524-1.53) 0.327 (-0.625-1.278) 0.34 (-0.469-1.15) 0.204 (-0.365-0.773)