#VisualAbstract: Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD Increases Risk of Major Cardiovascular Events and Mortality

1. Stopping renin-angiotensin system inhibition in patients with advanced chronic kidney disease was associated with higher risk of mortality, major cardiovascular events, and lower risk of kidney replacement therapy.

Evidence Rating Level: 2 (Good)

Studies have shown that renin-angiotensin system inhibitors (RASi) are effective in delaying chronic kidney disease (CKD) progression. Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are integral to treating proteinuric CKD. However, it is unknown whether RASi are safe and effective in patients with advanced CKD, or with eGFR <30mL/min/1.73m². While continuing RASi could accelerate the need for kidney replacement therapy (KRT), stopping RASi may impact its cardioprotective and mortality benefits. In this observational study, 10 254 patients from the Swedish Renal Registry, taking RASi for more than 80% of the 2 years before January 1, 2007 and with new-onset CKD G3-5, were included. Researchers emulated a target trial with a 5 year follow-up, using techniques such as cloning, censoring, and weighting, to compare the effects of stopping RASi within 6 months after eGFR dropped below 30mL/min/1.73m² compared to continuing RASi. From this cohort (median age 72 years, median eGFR 23mL/min/1.73m²), 15% stopped RASi therapy within 6 months. RASi discontinuation was associated with an increase in both absolute 5-year risk of death (54.5% vs 40.9%, ARD 13.6) and in major adverse cardiovascular events (59.5% vs 47.6%, ARD 11.9) over those who continued RASi treatment. However, stopping RASi therapy was also associated with a lower risk of KRT (27.9% vs 36.1%, ARD -8.3). These results remained consistent regardless of whether patients stopped RASi at an eGFR higher or below 20mL/min/1.73m², after adjusting and stratifying for albuminuria and potassium, and after modelling RAS inhibition as a time-dependent exposure on a marginal structural model. This study supports that the decision to stop RAS inhibition in patients with advanced CKD should be made after evaluating cardiovascular and KRT risk. Variables not captured in this trial include the reason for RASi discontinuation, such as patient frailty, and variation in practitioner behaviour: for example, the initiation of KRT itself is a treatment decision. Further study, especially randomized trials, should be conducted in order to support these observational findings.

Click to read the study in JASN

Image: PD

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