Differential Impact of Metoprolol Formulations on Heart Failure Outcomes: A Multicenter Study

<h2>ABSTRACT</h2><h3>Background</h3> Despite widespread use of metoprolol formulations in heart failure (HF), direct comparative evidence of their clinical outcomes remains limited. <h3>Methods</h3> In this retrospective cohort study using the TriNetX Research Network (2010-2024), we compared outcomes between metoprolol succinate and tartrate in HFrEF (EF ≤40%) and HFmrEF (EF 41-49%) patients. After propensity score matching (761 pairs for HFrEF, 732 pairs for HFmrEF), we evaluated a primary composite outcome of hospitalizations and all-cause mortality, and secondary outcomes of individual components over one year follow-up. <h3>Results</h3> Baseline characteristics were well-balanced between cohorts in both HF populations. For the primary composite outcome, both HFrEF and HFmrEF patients receiving succinate formulation demonstrated significantly better event-free survival compared to tartrate (HFrEF: 64.12% vs 51.22%, log-rank p<0.001; HFmrEF: 67.57% vs 56.04%, log-rank p<0.001). Secondary analysis revealed these benefits were driven by improvements in both hospitalizations and all-cause mortality. <h3>Conclusions</h3> Metoprolol succinate was associated with significantly improved event-free survival compared to tartrate in Kaplan-Meier analyses for both HFrEF and HFmrEF populations, despite modest differences in crude event rates. These findings suggest that formulation-specific pharmacokinetics influence long-term outcomes in heart failure management, supporting current guidelines favoring succinate over tartrate.