Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study

Abstract

Aims: The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China.

Methods and results: This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P < 0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P < 0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P < 0.001] during 12 month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P < 0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up.

Conclusions: Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Keywords: Dose titration; Heart failure; Management; Sacubitril/valsartan; Ventricular remodelling.