ARNI vs RASi in Older Adults With HFrEF Not Linked to Higher Rates of AKI

In a large cohort of US Medicare beneficiaries with heart failure with reduced ejection fraction (HFrEF), hospitalization rates for acute kidney injury (AKI) are similar among patients newly initiating an angiotensin receptor neprilysin inhibitor (ARNI) compared with those newly initiating a renin-angiotensin system inhibitor (RASi), according to the results of a study published in the Journal of Cardiac Failure.

Researchers conducted a new-user, active-comparator cohort study using US Medicare fee-for-service claims data between 2014 and 2017.  The researchers used data from Medicare Part A (hospitalizations), Part B (medical services), and Part D (prescription medications) claims.

The researchers enrolled patients with HFrEF who were aged 65 years or older who were newly initiating ARNI or RASi therapy, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, who reported no previous use of either drug class. The primary outcome was hospitalization for AKI, with AKI listed as the primary diagnosis at discharge. The secondary outcome included AKI as either a primary or a secondary diagnosis at discharge. Risks for AKI were described under an as-treated follow-up approach, with censoring on treatment discontinuation, switch, insurance disenrollment, death or administrative censoring, as well as under an intention-to-treat approach.

Among 9.2 million individuals with 1 or more filled prescription for sacubitril/valsartan or RASi, a total of 27,166 patients were included in the study. The cohort comprised 4155 participants initiating ARNI and 23,011 initiating RASi. The mean patient age was 73 (SD, 7.3) years. The majority of participants were men and White.

Results of the study showed that, over a median follow-up of about 4 months in the as-treated follow-up approach for ARNI initiators, a total of 90 primary outcome events and 214 secondary outcome events were reported. With the as-treated follow-up scheme, following propensity score-weighting, the estimated 180-day cumulative incidence for the primary outcome was 2.7% (95% CI, 2.4%-3.1%) in RASi initiators vs 2.7% (95% CI, 2.2%-3.5%) in ARNI initiators, and 6.5% (95%% CI, 6.0%-7.1%) vs 6.1% (95% CI, 5.2%-7.1%), respectively, for the secondary outcome.

Hazard ratios that compared ARNI with RASi were 0.91 (95% CI, 0.72-1.16) for the primary outcome and 0.92 (95% CI, 0.79-1.08) for the secondary outcome. With the intention-to-treat scheme, similar results were reported.

Several limitations of the study include possible misclassification of HFrEF and AKI in the analysis, as the investigators depended on ICD codes to identify the diagnoses. Additionally, residual confounding associated with factors not measured in administrative claims may exist. These findings also may not apply to patient populations that are not well represented in Medicare.

 “These results may reassure clinicians about early changes in renal function when considering initiation of ARNI without prior demonstrated tolerance to RASi,” the study authors wrote.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.