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Quit Angiotensin Meds When Kidney Function Worsens? Not So Fast

People on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) did well to stay the course even when kidney function dropped, researchers found in a retrospective study.

Clinical outcomes were worse among patients who stopped ACE inhibitors or ARB therapy in the 6 months after estimated glomerular filtration rate (eGFR) fell below 30 mL/min/1.73 m2, as Morgan Grams, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues reported in JAMA Internal Medicine.

Compared with staying on these medications, those who stopped had greater risk of mortality in the subsequent 2.9 years (HR 1.39, 95% CI 1.20-1.60) and more major adverse cardiovascular events in the subsequent 2.7 years (HR 1.37, 95% CI 1.20-1.56).

Notably, there was no lower risk of progression to end-stage kidney disease in the subsequent 2.7 years with stopping these meds (HR 1.19, 95% CI 0.86-1.65).

“Similar patterns held for individuals with a 40% or greater decrease in eGFR,” the group wrote.

The observational study provides “strong evidence that continuing ACE inhibitor/ARB therapy as tolerated in typical patients with CKD with declining kidney function does not lead to harm and is associated with reduced mortality,” according to Colette DeJong, MD, of the University of California San Francisco, and Richard Grant, MD, MPH, of Kaiser Permanente Northern California in Oakland.

The upcoming STOP-ACEi trial will be notable for providing randomized data on how its 410 patients with advanced renal disease fare after stopping ACE inhibitors and ARBs, DeJong and Grant wrote in an accompanying editor’s note.

ACE inhibitors and ARBs are established treatments for hypertension, heart failure with reduced ejection fraction, and coronary artery disease. However, conflicting evidence in the literature has made it unclear if these therapies should be used in individuals with advanced CKD, the investigators noted.

Grams’ team studied 3,909 patients (61.6% women, mean age 73.7) from the large Geisinger Health System in Pennsylvania. All initiated ACE inhibitor or ARB therapy in 2004-2018 and had eGFR fall below 30 mL/min/1.73 m2 afterward.

Study authors ended up with 2,410 individuals for analysis after propensity score matching of people who did and did not discontinue therapy.

While the two groups were similar in baseline covariates and despite the propensity score matching, the observational nature of the study made it susceptible to residual confounding, Grams and colleagues acknowledged.

“Because the clinical rationale for ACE inhibitor/ARB discontinuation, such as hyperkalemia or overall clinical trajectory, was not captured in the data source, there may have been unmeasured differences in health status between the groups that could partially explain the increased mortality among patients whose ACE inhibitor/ARB therapy was discontinued,” DeJong and Grant suggested.

Additionally, a mostly white study population limited the generalizability of the results. Other limitations of the study were inference of ACE inhibitor or ARB use through prescription records and that many patients who discontinued therapy actually then restarted therapy during follow-up.


The study was supported by NIH grants.

Grams disclosed travel support from Dialysis Clinics.

DeJong and Grant listed no conflicts of interest.