Should We Retain Half-Dose ARNIs in HFrEF? Lessons Learned from Reverse Remodeling using CORE-HF Real-World Data

Background: Heart failure (HF) is a progressive health problem with high mortality and morbidity rates in both developed and developing countries. Patients with HF who develop reverse remodeling during treatment have better outcomes and lower mortality. Real-world data on the reverse remodeling effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor-neprilysin inhibitors (ARNIs) in Indonesians are yet to be available.

Objectives: This study aimed to compare the reverse cardiac remodeling of patients with heart failure with reduced ejection fraction (HFrEF) treated for six months with an ARNI or ACEI based on the CORE-HF registry.

Methods: We conducted a non-experimental, sub-analysis study of the CORE-HF database at the Heart Failure Clinic of Universitas Sebelas Maret Hospital from 2018 to 2021. One group had been treated with ARNIs, while the other was administered with the optimal tolerated ACEI. A six-month follow-up was carried out to determine left ventricle reverse remodeling (LVRR) and functional class alteration as endpoints.

Results: While 89.2% of those in the ACEI group could tolerate the maximum dose, only one person in the ARNI group received the maximum dose, with the majority receiving half the maximum dose (100 mg BID). After six months, LVRR occurred at a similar rate in both groups (26.31% for ARNI and 26.15% for ACEI; P = 0.989). However, the New York Heart Association functional class improved more in the ARNI group (mean 0.95 ± 0.7 vs. 0.62 ± 0.86; P = 0.128).

Conclusions: Despite similar LVRR and functional capacity improvements, a slightly better echocardiography improvement was observed in the ACEI arm. We postulate that full intervention of the renin-angiotensin-aldosterone system should still be the main goal, together with other guideline-directed medical therapies for HF. Hence, cost-effective full-dose of ACEi should be chosen for low- to middle-income countries whose ARNI was not easily available yet due to several issues.