On-Treatment Blood Pressure and Dose-Dependent Effects of ARNI in Heart Failure with Reduced Ejection Fraction: Insights from a Multicenter Registry

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Abstract Achieving the target dose of angiotensin receptor-neprilysin inhibitor (ARNI) in heart failure with reduced ejection fraction (HFrEF) remains challenging due to concerns related to hypotension. This study investigated the dose-dependent effects of ARNI based on on-treatment blood pressure (BP). Using 1,097 HFrEF patient data from a multicenter HF registry who received ARNI for at least 6 months, subjects were stratified into low-dose (<100 mg/day; n=249) and intermediate- to high-dose (≥100 mg/day; n=848) groups based on the average ARNI dose over a 1-year period. Changes in echocardiographic features and clinical outcomes were assessed, considering on-treatment BP profiles (high-BP [average systolic BP ≥110 mmHg] and low-BP [<110 mmHg]). Low-BP was an independent predictor for low-dose ARNI. Echocardiographic improvements were observed in both dose groups, with more pronounced changes in the intermediate- to high-dose group. Over a median follow-up of 3.1 years, the low-dose group demonstrated an increased risk of mortality compared to the intermediate- to high-dose group. These trends were consistently observed in both BP profiles. In conclusion, low-dose ARNI leads to insufficient improvements in echocardiographic parameters and worse clinical outcomes regardless of on-treatment BP, suggesting the importance of optimal dose titration, which should not be discouraged by low-BP response.

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