Monday, June 21, 2021

Do ACE-Is and ARBs benefit patients with advanced CKD?

 - Jennifer Middleton, MD, MPH

Many prescribers discontinue patients' angiotension-converting enzyme inhibitors (ACE-Is) or angiotension receptor blockers (ARBs) as their estimated glomerular filtration rate (eGFR) worsens due to concerns about hyperkalemia, hypotension, and/or worsening chronic kidney disease (CKD). Slightly less than half of all persons with CKD stage 4 or 5 in the United States (US) are not currently prescribed an ACE-I or ARB. Two recent studies, however, demonstrate potential benefits of ACE-I and ARB use in patients with advanced CKD. 

The first study reviewed the medical records in a large US health system of nearly 4,000 patients with CKD who were prescribed an ACE inhibitor or an ARB and whose CKD eventually worsened to an eGFR below 30 mL/min/1.73m2. Cohorts were divided into patients whose ACE-Is or ARBs were discontinued when their eGFR dropped below 30 mL/min/1.73m2 and those patients whose ACE-Is or ARBs were continued despite this lower eGFR. Researchers then tracked participants' outcomes for 5 years. They found that persons who had their ACE-I/ARB discontinued had a higher mortality risk than those whose ACE-Is/ARBs were continued (hazard ratio [HR] 1.39; 95% CI 1.20-1.60). The risk of adverse cardiac events was higher in persons who had stopped their ACE-I/ARB (HR 1.37; 95% CI 1.20-1.56). There was no difference in the rate of CKD progression to end-stage kidney disease (ESKD) between groups (HR 1.19; 95% CI 0.86-1.65).

The second study reviewed the medical records of nearly 5000 patients in Sweden with an eGFR below 30 mL/min/1.73m2 (but not receiving dialysis) who received a new prescription for either an ACE-I/ARB or a calcium channel blocker (CCB). After a median of 4.1 years, persons who received an ACE-I/ARB had a lower risk of needing to initiate dialysis compared to the persons who received a CCB (adjusted HR, 0.79 [95% CI, 0.69-0.89]). Mortality and risk of adverse cardiac events were similar in both groups (adjusted HR, 0.97 [95% CI, 0.88-1.07] and adjusted HR, 1.00 [95% CI, 0.88-1.15]), respectively). 

These two studies examined different nuances of patients with advancing CKD: the first, persons whose previous ACE-I/ARB was continued despite worsening eGFR, the second, persons receiving new prescriptions for ACE-I/ARB at a lower eGFR. These differences may explain the studies' differing findings regarding mortality benefit of these medication classes (only found in the first study), adverse cardiac events benefit (the first study), and lowered risk of advancement to ESKD (the second study).

Cohort studies can only demonstrate correlation. Both studies' authors acknowledge the potential for unrecognized confounding factors; for example, it's possible that the persons in both studies who didn't receive ACE-Is/ARBs were somehow more ill than those who did. Until we see randomized controlled trials comparing these approaches, though, these current studies are the best evidence we have to date, and they suggest that continuing ACE-I/ARBs in persons with advanced CKD is likely safe and may have benefits.

If you'd like to read more, check out the AFP By Topic on Kidney Disease, which includes this article on "Chronic Kidney Disease: Detection and Evaluation" and this Cochrane for Clinicians on "ACE Inhibitors vs. ARBs for Patients with Diabetic Kidney Disease."