Stopping renin-angiotensin system inhibitors show benefits, risks in advanced CKD
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Researchers from the Netherlands have identified benefits and risks associated with stopping renin-angiotensin system inhibitor therapy in patients with advanced chronic kidney disease.
“Whether renin-angiotensin system (RAS) inhibition is safe and effective in patients with advanced CKD is unknown,” Edouard L. Fu, BSc, of Leiden University Medical Center, and colleagues wrote. “Single-center studies suggest there is improved kidney function after stopping [renin-angiotensin system] RAS inhibition and possible delay in initiating kidney replacement therapy (KRT), but large prospective studies assessing cardiovascular and kidney outcomes are lacking.”
For the study, researchers included 10,254 Swedish adults who developed advanced CKD while on RASi therapy (median age, 72 years; 36% women). Of these, 15% stopped the therapy within 6 months. Researchers compared outcomes of these patients to those who continued therapy.
Results showed that, compared with continuing RAS inhibition, stopping therapy was associated with a higher absolute 5-year mortality risk (40.9% vs. 54.5%) and major adverse cardiovascular events (47.6% vs. 59.5). However, stopping therapy was also associated with a lower risk of kidney replacement therapy (36.1% vs. 27.9%).
“Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model,” Fu and colleagues wrote, noting that because the conclusions are observational, these do not “substitute for randomized trials.”
“However, until these trials are conducted, our findings may assist in informing clinical decisions,” they concluded.
Perspective
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The Fu and colleagues’ study compares the death, major cardiovascular events and initiation of kidney replacement therapy (KRT) after stopping vs. continuing renin-angiotensin system inhibition (RASi) in advanced CKD patients (eGFR <30 mL/min. per 1.73 m2). This study observes 8.3 KRT events could be prevented per 100 patients who continued with RASi therapy over 5 years. They conclude that stopping RASi treatment was associated with a higher 5-year risk of mortality and MACE, while absolute KRT risk was higher with lower eGFR.
The RASi reduces cardiovascular risk and delays CKD progression, especially in diabetic nephropathy. Although in advanced CKD patients, RASi often is stopped due to hyperkalemia or worsening creatinine. The overall benefit of RASi in CKD remains unexplored. As per this study results, composite clinical benefits, including death and KRT being equivalent, suggest RASi therapy continuations. The previous observational study, like this, shows similar outcomes in delaying KRT. However, there is a lack of prospective clinical data verifying the clear-cut cardiovascular benefit and impact of CKD.
Given current evidence, the patient priorities should be considered before the therapy changes, especially when complications arise. The patients may prioritize delaying KRT over death, especially with overall high mortality secondary to other comorbidities.
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