Renin-angiotensin system (RAS) inhibitors are useful for slowing the progression of mild-to-moderate chronic kidney disease (CKD). Some studies have suggested that stopping the agents when CKD becomes more advanced might be beneficial. Now, a new study supports stopping the drugs, showing no difference in the decline in estimated glomerular filtration rates (eGFRs) when ACE inhibitors and ARBs were discontinued in patients with advanced CKD.
In a multicenter, open-label trial, patients with advanced and progressive CKD (eGFR, <30 mL/min) were randomized to either to discontinue or continue therapy with RAS inhibitors. Based on a primary outcome of the eGFR at 3 years and other secondary outcomes, STOP ACEi trial investigators found: “At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m2 in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m2 in the continuation group (difference, −0.7; 95% confidence interval [CI], −2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. [End-stage kidney disease] or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22).”
Editorial: “What should we do as practitioners in choosing to continue or stop RAS inhibitors in patients with advanced CKD?” editorialists ask. “First, we must weigh whether data from the STOP-ACEi trial apply to the given patient, especially since all the trial patients were receiving RAS inhibitors and the trial was open label and limited mainly to White patients in midlife. How we should interpret the trial results in patients who have not been receiving RAS inhibitors or have not taken them consistently is unclear. Second, many of our patients will probably be receiving other kidney-protective medications, such as SGLT2 inhibitors or GLP-1 agonists, which were not being evaluated in patients with CKD when this trial began. The use of newer therapies for hyperkalemia with fewer side effects means that concerns about the development of adverse events related to potassium levels may be somewhat mitigated. In all, each patient and each clinician will best reach a mutual decision about the continuation or discontinuation of RAS inhibitors through consideration of specific risks and individual preferences. That being said, the STOP-ACEi trial provides important data that have been lacking until now.”