Heterogeneous benefit of early sacubitril/valsartan initiation after PCI in elderly patients with left ventricular dysfunction: myocardial recovery and mid-term cardiovascular outcomes

Background: The optimal timing of sacubitril/valsartan initiation after percutaneous coronary intervention (PCI) in elderly patients with left ventricular dysfunction remains unclear. This study evaluated whether very early initiation was associated with better myocardial recovery and clinical outcomes than delayed initiation or no sacubitril/valsartan. Methods: In this single-center retrospective cohort study, elderly patients with left ventricular dysfunction after successful PCI were classified into three groups according to treatment timing: early initiation (≤7 days), delayed initiation (14-28 days), and no sacubitril/valsartan. After 1:1:1 propensity score matching, 360 patients were included. Echocardiographic recovery and biomarker changes were assessed at 8 weeks, and major adverse cardiovascular events (MACE) were evaluated over 12 months using competing-risk analysis. Results: In the matched cohort, the early initiation group showed the greatest improvement in left ventricular ejection fraction and cardiac index, together with the largest reductions in left ventricular dimensions at 8 weeks. Early initiation was also associated with more favorable declines in inflammatory and cardiac injury biomarkers, including hs-CRP and NT-proBNP. During 12-month follow-up, MACE occurred in 8.3% of the early group, 20.8% of the delayed group, and 25.0% of the control group. In Fine-Gray models, early initiation was associated with a significantly lower risk of MACE than delayed initiation and no sacubitril/valsartan. Exploratory subgroup analyses suggested stronger associations in patients aged ≥75 years and those with baseline LVEF ≤40%. Safety outcomes were comparable across groups. Conclusions: In this propensity score-matched retrospective analysis of elderly patients with left ventricular dysfunction after PCI, initiation of sacubitril/valsartan within 7 days was associated with more favorable short-term myocardial recovery profiles and a lower 12-month cardiovascular risk compared with delayed initiation or no ARNI therapy. However, residual confounding and potential immortal time bias cannot be excluded. These hypothesis-generating findings suggest a potential association that merits evaluation in prospective, randomized studies designed to compare different treatment timing strategies.