O1011: Sacubitril vs. ACE/ARB for Pediatric Heart Failure

Background: Among the newer therapies in heart failure management is inhibition of neprilysin, which is responsible for the breakdown of multiple peptides including BNP. By inhibiting neprilysin, the diuretic and blood pressure effect of BNP is sustained. Sacubitril is the only medication in this class available in the United States, and was approved for adult heart failure based on data showing a 20% reduction in death from cardiovascular causes or hospitalization for heart failure. Despite the absence of any published comparator studies of sacubitril in pediatric heart failure, it is being used nationwide. A large trial of sacubitril in pediatric heart failure is ongoing, however enrollment was limited to patients with a failing systemic left ventricle, and will not be generalizable to many pediatric heart failure patients. We sought to describe the effect of sacubitril use on outcomes in a broader pediatric heart failure cohort.

Methods: Using deidentified data from TriNetX, a globally federated research network, we identified patients under the age of 21 years who had been diagnosed with heart failure by ICD-10 code, and prescribed either sacubitril (sacubitril cohort) or an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker without use of sacubitril (ACE/ARB cohort), during or after 2015. Propensity score matching was used to identify a subset of the ACE/ARB cohort to serve as the comparator, based on a number of variables. (Table 1)

The primary outcome was the rate of all-cause mortality or heart transplantation within one year, and secondary outcomes were the rates of hypotension, renal dysfunction, hyperkalemia, or hospitalization. Patients with the outcome in question in the prior year were excluded from the analysis for that outcome.

Results: We identified 559 patients prescribed sacubitril and 8,407 prescribed an ACE/ARB. After propensity score matching, all characteristics were similar between both groups. (Table 1) The primary composite outcome of all-cause mortality or heart transplantation within 1 year occurred in 13.3% of the sacubitril cohort and in 13.2% of the ACE/ARB cohort (p=0.95). There was a trend toward reduction in hospitalizations associated with sacubitril (mean 1.3 vs. 2.0; p=0.09), and a significant increase in hypotension diagnoses (10.3% vs. 5.2%, p=0.006), though no difference in hyperkalemia or renal dysfunction was observed. (Table 2) At the end of one year, 92 of 519 patients (17.7%) in the sacubitril cohort had been subsequently prescribed an ACE/ARB other than valsartan.

Conclusion: In a propensity score matched, retrospective analysis of pediatric patients with heart failure treated with either sacubitril or an ACE/ARB, sacubitril was not associated with a difference in the composite of all-cause mortality or heart transplantation, nor either of the components alone, but may be associated with decreased hospitalizations and increased hypotension.