Renin-angiotensin system inhibitors may lower CV, mortality risk in kidney disease
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Patients with chronic kidney disease and declining kidney function who received angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy were at lower risk for major adverse CV events and mortality, according to a retrospective cohort study published in JAMA Internal Medicine.
The Kidney Disease Improving Global Outcomes guideline recommends temporarily stopping angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) therapy in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 who “have serious intercurrent illness that increases the risk of acute kidney injury,” Yao Qiao, MPH, an MHS and PhD candidate at the department of epidemiology at Johns Hopkins University Bloomberg School of Public Health, and colleagues wrote.
However, the guideline also states that patients with eGFR of less than 30 mL/min/1.73 m2 should “not routinely discontinue ACE-I/ARB as they remain nephroprotective,” they added.
The researchers said the existing literature evaluating the risks vs. benefits of ACE-I or ARB therapy in patients with advanced CKD is “conflicting.” To resolve the discrepancies, they compared outcomes in 3,909 patients (mean age, 73.7 years; 62% women) who received ACE-I or ARB treatment and had their eGFR drop below 30 mL/min/1.73 m2. Of the entire cohort, 1,235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease, whereas the remaining patients remained on the therapy.
During the trial, there were 1,220 patients (434 who discontinued ACE-I or ARB therapy and 786 who did not discontinue therapy) who died during a median follow-up of 2.9 years (interquartile range, 1.3-5). Researchers found that among a propensity score-matched sample of 2,410 patients, ACE-I or ARB therapy discontinuation was linked to a higher risk for mortality (HR = 1.39; 95% CI, 1.2-1.6) and major adverse CV events (HR = 1.37; 95% CI, 1.2-1.56) but no statistically significant difference in risk for end-stage kidney disease (HR = 1.19; 95% CI, 0.86-1.65). In additional analysis, 1,205 patients (98%) who discontinued therapy were matched with controls — a total patient sample of 2,410 individuals.
“The findings were robust to a number of sensitivity analyses, including using a target trial emulation technique and excluding individuals with hypotension, hyperkalemia, acute kidney injury or a history of cancer at the time of the eGFR decrease,” Qiao and colleagues wrote. “ACE-I or ARB therapy discontinuation was associated with a lower risk of hyperkalemia, consistent with existing evidence; however, this risk did not appear to outweigh the potential cardiovascular and survival benefits of continuing ACE-I or ARB therapy.”
In a related editorial, Colette DeJong, MD, MS, a physician of the department of medicine at the University of California, San Francisco, and Richard W. Grant, MD, MPH, a research scientist at Kaiser Permanente Northern California, wrote that the evidence Qiao and colleagues gathered is “strong,” but there are limitations to it.
“Because the clinical rationale for ACE-I/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-I/ARB therapy was discontinued,” DeJong and Grant wrote.
They said additional data could “better establish the cause and effect” seen in Qiao and colleagues’ study. – by Janel Miller
Disclosures: DeJong, Grant and Qiao report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.