Stopping renin-angiotensin-system (RAS) inhibitor therapy increases the risk for death and major adverse cardiovascular events (MACE) in patients with advanced chronic kidney disease (CKD), even in those with elevated serum potassium levels, a new nationwide study of Swedish patients confirms. But the new report also documents an increased risk for kidney replacement therapy (KRT). 

Compared with continuing RAS inhibition (RASi), stopping angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy was associated with a higher absolute 5-year risk of all-cause mortality (54.5% vs 40.9%) and MACE (59.5% vs 47.6%), but with a lower risk of KRT (27.9% vs 36.1%), Edouard L. Fu, an MD/PhD student at Leiden University Medical Center in The Netherlands, and colleagues reported in the Journal of the American Society of Nephrology. That amounts to an excess 13.6 deaths and 11.9 MACEs per 100 patients over 5 years.

Results were consistent whether patients stopped RAS inhibitors early at an estimated glomerular filtration rate (eGFR) of 20 to 30 mL/min/1.73 m2 or later at an eGFR less than 20 mL/min/1.73 m2. The findings were also consistent among patients with baseline albuminuria above and below 70 mg/mmoL or serum potassium above and below 5.0 mmol/L.

The investigators used data from 10,254 prevalent RAS inhibitor users (median age 72 years; 36% female) whose eGFR newly declined to less than 30 mL/min/1.73 m2 to create target trial emulation and marginal structural models. Of the cohort, 1553 (15%) stopped RAS inhibitor therapy within 6 months of kidney function decline.


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The findings largely corroborate results from a JAMA Internal Medicine study of more than 3000 US patients published in 2020. But the current study found an increased risk for KRT among discontinuers of RAS inhibitors. In an analysis assuming death and dialysis are of equal importance, results favored RAS inhibitor continuation. The investigators emphasized that individual preferences should be incorporated in decision-making.

“To date, there is no trial evidence to inform the decision of stopping RASi therapy in these patients,” Dr Fu’s team stated. “Until the ongoing STOP-ACEi trial is completed, our analyses support current Kidney Disease Improving Global Outcomes’ recommendations of not routinely stopping RASi in people with advanced CKD.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Fu EL, Evans M, Clase CM, et al. Stopping renin-angiotensin system inhibitors in patients with advanced CKD and risk of adverse outcomes: a nationwide study. J Am Soc Nephrol. doi:10.1681/ASN.2020050682