No Excess Risk of Kidney Injury for ARNI Initiation in RASi Naive Patients

Ankeet Bhatt, MD

New research presented at the Heart Failure Society of America (HFSA) 2022 annual scientific meeting is providing clinicians with insight into the potential risk for acute kidney injury among older adults with heart failure being treated with a newly initiated angiotensin-neprilysin inhibitor (ARNI) compared to a renin-angiotensin system inhibitor (RASi).

An analysis of Medicare fee-for-service claims data from patients with heart failure with reduced ejection fraction (HFrEF), result of the study, which were presented by Ankeet Bhatt, MD, of Kaiser Permanente Northern California, provide evidence suggesting new initiators of ARNI therapy experienced similar hospitalization rates for acute kidney injury as their counterparts receiving RASi.

“Among a large cohort of US Medicare beneficiaries with HFrEF, ARNI treatment was not associated with higher rates of AKI than RASi. These results provide reassurance for providers considering ARNI initiation in older patients who are RASi naïve,” wrote investigators.

Although ARNI has become included in guideline-directed medical therapy for HFrEF, real-world uptake of the class has lagged behind, inhibiting its potential impact on a population level. Many of these concerns are related to cost or effectiveness of the agent but given the early impact on kidney function observed in clinical trials, some have expressed concerns over potential risk of acute kidney injury. With this in mind, Bhatt along with Muthiah Vaduganathan, MD, MPH, and a team of colleagues from Boston-based institutions, including Brigham and Women’s Hospital and Harvard Medical School, launched the current research endeavor with the intent of comparing rate of acute kidney injury among new initiators of ARNI or RASi considered RASi naïve at the time of initiation.

Using Medicare FFS claims from 2014-2017, the study aggregated data from more than 27,166 Medicare Beneficiaries aged 65 years or older with HFrEF and initiating either of the aforementioned therapies. Overall, the cohort had a mean age of 73 (SD, 7.3) years, with 4155 new initiators of ARNI and 23,011 new initiators of RASi.

The primary outcome of tinniest for the analysis was the incidence of hospitalization with acute kidney injury as the primary discharge diagnosis. The secondary outcome of interest was incidence of acute kidney injury as a primary or secondary discharge diagnosis. Investigators noted propensity-score-based fine-stratification weighting was used to account for potential confounding by 81 preexposure characteristics and Vox proportional hazards were used to provide hazard ratios for the study outcomes.

In propensity-score-based analyses, the 180-day cumulative incidence of the study’s primary outcome was 2.7% (2.4-3.1%) among RASi initiators compared to 2.7 (2.2-3.5%) among ARNI initiators. When assessing the secondary outcome, the rate of incidence was 6.5% (6.0-7.1%) for RASi initiators and 6.1% (5.2-7.1%) for ARNI initiators. Further analysis indicated the risk for both the primary outcome (HR, 0.91 [95% CI, 0.72-1.16]) and the secondary outcome (HR, 0.92 [95% CI, 0.79-1.08]) were not increased with ARNI initiation compared to RASi initiation. Investigators noted similar results were observed in intent-to-treat analyses.

This study, “Risk Of Acute Kidney Injury Among Older Adults With Heart Failure Treated With Angiotensin-neprilysin Inhibitor Versus Renin-angiotensin System Inhibitor In Routine Clinical Care,” was presented at HFSA 2022 and simultaneously published in the Journal of Cardiac Failure.