Study sheds new light on RAS inhibitors’ role for advanced CKD

ORLANDO – Treatment with a renin-angiotensin system (RAS) inhibitor is widely accepted as standard practice for slowing progression of chronic kidney disease (CKD), but data have been inconsistent as to whether there is benefit to continuing RAS inhibition when patients develop advanced CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m².

Now, in STOP ACEi, a new multicenter, randomized trial of 411 patients, maintaining treatment with a RAS inhibitor in adults with advanced and progressive CKD did not cause a clinically relevant change in kidney function, or in the long-term rate of decline in kidney function, compared with stopping treatment, for 3 years.

People who continued RAS inhibitor treatment did not develop a significant or clinically relevant decrease in eGFR, the study’s primary outcome, both overall as well as in several prespecified subgroups compared with those who discontinued treatment, said Sunil Bhandari, MBChB, PhD, and associates, who presented the research in a poster at the annual meeting of the American Society of Nephrology.

“I hope these results will reassure clinicians to continue ACE inhibitors or ARBs” in patients with advanced CKD, “with their known beneficial cardiovascular effects,” Dr. Bhandari said in an interview.

The results were simultaneously published in the New England Journal of Medicine.

Similar eGFR levels after 3 years

While it’s clear that in patients with mild or moderate CKD, treatment with a RAS inhibitor, which includes angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), reduces blood pressure, slows decline in eGFR, reduces proteinuria, and delays progression to advanced CKD, there has been little evidence that the use of RAS inhibitors benefits patients with advanced CKD.

Data from previous trials have been inconsistent regarding whether the use of RAS inhibitors is nephroprotective in patients with advanced CKD, say Dr. Bhandari, a nephrologist and professor at Hull York Medical School, Hull, England, and colleagues.

“Current guidelines do not provide specific advice on whether to continue or stop ACE inhibitors or ARBs for advanced chronic kidney disease,” they also note.

And so they decided to assess whether discontinuation of ACE inhibitors/ARBs could slow progression of CKD in patients with advanced CKD.

Three years after 206 study participants stopped RAS inhibitor treatment, the least-squares mean eGFR was 12.6 mL/min per 1.73m² in the discontinuation group and 13.3 mL/min per 1.73 m² in the 205 patients in the continuation group, a difference that was not significant.

In addition to the primary outcome, 62% of patients who stopped RAS inhibitor treatment and 56% of those who continued developed end-stage kidney disease or required renal-replacement therapy, which translated into an adjusted hazard ratio of 1.28 for this outcome among those who discontinued compared with those who continued, which was just short of significance (95% CI, 0.99-1.65).

The two study groups also showed no significant differences in the 3-year incidence of hospitalization for any reason, cardiovascular events, or deaths. The two groups also showed no meaningful differences in various domains of quality of life and no differences in serious adverse effects.