Discontinuing therapy with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) when estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73 m² increases the risk for mortality and major adverse cardiovascular events (MACE), according to new study findings published online in JAMA Internal Medicine.

In an analysis of 2410 propensity-score matched users of renin-angiotensin system (RAS) blockade who experienced kidney function decline to less than 30 mL/min/1.73 m², discontinuation of the hypertension medications was significantly associated with 39% and 37% increased risks for all-cause mortality and MACE, respectively, over 5 years of follow-up compared with continuation, Morgan E. Grams, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues reported. They found no statistically significant differences in the risks for end-stage kidney disease or acute kidney injury.

A smaller proportion of patients who discontinued ACE-I or ARB therapy experienced hyperkalemia: 15.6% vs 22.2%. After propensity-score matching, discontinuation was associated with a 35% lower risk of hyperkalemia. This risk did not appear to outweigh the potential benefits of continuing therapy, however, according to the authors.

“Our findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may provide cardiovascular and survival benefits without excess risks of ESKD,” Dr Grams’ team stated.

In the observational study, the investigators examined a cohort of 3909 users of ACE-I or ARB from a Pennsylvania healthcare system (62% female; less than 2% black; mean age 74 years) who progressed to stage 4 or 5 chronic kidney disease. Of these, 1235 discontinued ACE-I or ARB therapy within 6 months of the drop in eGFR and 2674 did not. During a median 2.9 years, 35.1% of patients who discontinued therapy and 29.4% who continued therapy died.

In an accompanying editorial, Colette DeJong, MD, MS, of the University of California, San Francisco, and Richard W. Grant, MD, MPH, of Kaiser Permanente Northern California in Oakland, praised the new study, saying it provides useful data and “strong evidence that continuing ACE-I/ARB therapy as tolerated in typical patients with chronic kidney disease with declining kidney function does not lead to harm and is associated with reduced mortality.”

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

References

Qiao Y, Shin JI, Chen TK, et al. Association between renin-angiotensin system blockade discontinuation and all-cause mortality among persons with low estimated glomerular filtration rate [published online March 9, 2020]. JAMA Intern Med. doi: 10.1001/jamainternmed.2020.0193

DeJong C, Grant RW. Continuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the face of kidney disease progression—safe and possibly life saving [published online March 9, 2020]. JAMA Intern Med. doi: 10.1001/jamainternmed.2020.0300