Abstract
BACKGROUND AND AIMS: Long-term real-world effects of sacubitril/valsartan (S/V) and the impact of S/V dose reduction or discontinuation are less defined. We assessed longitudinal changes after S/V initiation and the association of dose changes with major adverse cardiovascular events (MACE). METHODS: Multicentre retrospective study of 592 HFrEF outpatients starting S/V (83% men; age 68 ± 10 years; LVEF 32 ± 7%). NT-proBNP, Kansas City Cardiomyopathy Questionnaire (KCCQ) and echocardiography were collected at baseline, 12 months, and last follow-up. MACE was analysed with Kaplan-Meier and Cox models. RESULTS: NT-proBNP decreased from 1000 (494-2333) to 751 (304-1726) and 735 (215-1980) pg/ml (P < .001). KCCQ improved from 53 ± 15 to 62 ± 14 and 66 ± 15 (P < .001). LVEF increased from 32 ± 7 to 36 ± 8 and 37 ± 9% (P < .001) and GLS improved from -10.8 ± 3.2 to -12.3 ± 3.1 and -14.0 ± 2.9% (P < .001). During a median follow-up of 3.72 years, 225 patients (38%) experienced MACE (36 deaths; 134 HF hospitalizations). MACE incidence was higher in patients with S/V discontinuation and with dose reduction (log-rank P = .013 and P = .014). In multivariable Cox analysis, S/V discontinuation [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.28-1.97; P = .040], change in GLS (HR 0.81, 95% CI 0.67-0.98; P = .028) and change in KCCQ (HR 0.95, 95% CI 0.92-0.98; P = .001) were independently associated with MACE. CONCLUSIONS: S/V initiation was associated with sustained improvements in NT-proBNP, quality of life, and cardiac remodelling. S/V discontinuation or dose reduction identified patients at higher MACE risk.