Long-term outcomes following sacubitril/valsartan therapy for chronic HFrEF: an Italian real-world multicentre study
Giuseppe Dattilo1, Roberto Licordari1, Egidio Imbalzano2
1Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Cardiology, University of Messina, Messina, Italy.
Insights
Sacubitril/valsartan (S/V) improves heart failure metrics and quality of life. Discontinuing or reducing S/V dose increases the risk of major adverse cardiovascular events (MACE).
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- Long-term real-world data on sacubitril/valsartan (S/V) efficacy and impacts of dose modification are limited.
- Understanding these effects is crucial for optimizing heart failure management.
Purpose of the Study:
- To assess longitudinal changes in heart failure markers after initiating S/V.
- To evaluate the association between S/V dose reduction/discontinuation and major adverse cardiovascular events (MACE).
Main Methods:
- A multicenter retrospective study involving 592 patients with heart failure with reduced ejection fraction (HFrEF) initiating S/V.
- Collected data included NT-proBNP, Kansas City Cardiomyopathy Questionnaire (KCCQ), and echocardiography at baseline and follow-up.
- MACE were analyzed using Kaplan-Meier and Cox regression models.
Main Results:
- S/V initiation led to significant improvements in NT-proBNP levels, KCCQ scores, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS).
- Over a median follow-up of 3.72 years, 38% of patients experienced MACE.
- Higher MACE incidence was observed in patients who discontinued or reduced their S/V dose.
Conclusions:
- Sacubitril/valsartan (S/V) therapy is associated with sustained improvements in clinical markers and cardiac remodeling in HFrEF patients.
- S/V discontinuation or dose reduction is linked to an increased risk of MACE, highlighting the importance of treatment adherence.
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.
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