Key result
Pre-discharge target-dose ACE inhibitors linked to ~9% lower mortality in HFrEF versus lower doses.
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Why the study?
Whether the benefits of target-dose ACE inhibitors on reducing death and kidney failure in stable HFrEF patients extend to hospitalized patients with acute decompensated HF was uncertain.
Does inpatient initiation of target-dose ACE inhibitors reduce death or kidney failure in veterans with HFrEF compared to below-target doses?
Cohort (n=15,152)
Yes
Does inpatient initiation of target-dose ACE inhibitors reduce death or kidney failure in veterans with HFrEF compared to below-target doses?
Initiation of target-dose ACE inhibitors prior to hospital discharge in HFrEF patients is associated with a lower risk of death and is safe for kidney function, supporting more aggressive inpatient up-titration.
Target-dose ACEI at HFrEF discharge was associated with lower mortality; extends stable HF data but remains hypothesis-generating pending RCTs.
BACKGROUND: In patients with relatively stable heart failure with reduced ejection fraction (HFrEF), target doses of 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 dose due to hemodynamic instability and impaired kidney function, remains uncertain. METHODS: Of the 15,152 veterans with HFrEF (LVEF ≤40%) without baseline KF, who were hospitalized for acute decompensated HF between 2000 and 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 were 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. RESULTS: Matched patients (n=5768) had a mean (±SD) age of 66 (±12) years, LVEF 26% (±9%), estimated glomerular filtration rate 76 (±23) mL/min/1.73 m²; 99% were men, and 36% were African American. Patients in the 2 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 in 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, it was 0.90 (95% CI, 0.84-0.97). CONCLUSION: The observed renal safety and lower mortality rate in patients with HFrEF newly initiated on ACEIs at higher target doses before discharge support the use of this inpatient strategy and suggest that it may help to mitigate the persistent outpatient inertia in the initiation and up‑titration of evidence‑based HF therapies.
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Arundel et al. (2026) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=15,152). Target-dose ACE inhibitors vs. Below-target dose ACE inhibitors was evaluated on All-cause mortality (HR 0.91, 95% CI 0.85-0.98). Target-dose ACE inhibitor initiation before hospital discharge in patients with HFrEF was associated with a lower risk of death compared to below-target doses (HR 0.91; 95% CI, 0.85-0.98).
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