Inpatient Initiation of Target-Dose ACE Inhibitors and Lower Risk of Death or Kidney Failure in Veterans With HFrEF:...

In patients with relatively stable heart failure with reduced ejection fraction (HFrEF), target-dose angiotensin-converting enzyme inhibitors (ACEIs), compared with below-target doses, reduce the risks of death and kidney failure (KF). Whether these benefits extend to hospitalized patients, who are less likely to receive target doses due to hemodynamic instability and impaired kidney function, remains uncertain.

Of the 15,152 Veterans with HFrEF (LVEF ≤40%) without baseline KF, who were hospitalized for acute decompensated HF between 2000-2018 and newly initiated on ACEIs prior to discharge, 3143 (20.7%) received guideline‑recommended target doses. Propensity scores for the receipt of target-dose were calculated for each of the 15,152 patients and used to match 2884 (91.8% of 3143) target-dose patients to 2884 below-target-dose patients. Hazard ratios (HRs) for mortality and KF associated with target-dose ACEIs were estimated.

Matched patients (n=5768) had mean (±SD) age 66 (±12) years, LVEF 26% (±9%), eGFR 76 (±23) mL/min/1.73 m², 99% were men, and 36% were African American. Patients in the two dose groups were balanced on 76 baseline characteristics. During 5 years of follow‑up, all‑cause mortality occurred in 56.1% of below‑target‑dose patients and 52.6% of target‑dose patients. KF occurred in 4.2% and 3.6%, respectively. Target‑dose ACEIs were associated with a 9% lower risk of death (HR 0.91; 95% CI, 0.85-0.98). The HR for KF was 0.83 (95% CI, 0.64-1.08), and for the composite endpoint of KF or death was 0.90 (95% CI, 0.84-0.97).

The observed renal safety and lower mortality in patients with HFrEF newly initiated on ACEIs at higher target doses before discharge support the use of this inpatient strategy and suggest it may help mitigate the persistent outpatient inertia in the initiation and up‑titration of evidence‑based HF therapies.