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Differential Impact of Metoprolol Formulations on Heart Failure Outcomes: A Multi-center Study
Journal article   Open access

Differential Impact of Metoprolol Formulations on Heart Failure Outcomes: A Multi-center Study

Samuel A. Mensah, Patrick A. Kwaah, Abdulrahman Murshid, Frank Adusei-Poku, Maame Yaa Idun, Harsh Patel, Ademola Ajibade, Alex Kumi, Maan Awad, Olanrewaju Adeniran, …
Journal of Cardiac Failure - Intersections, Vol.2(1), pp.17-26
01/2026
DOI: 10.1016/j.yjcafi.2025.10.010
url
https://doi.org/10.1016/j.yjcafi.2025.10.010View
Published (Version of record) Open Access

Abstract

•First large-scale retrospective comparison of metoprolol succinate versus tartrate in heart failure with reduced (HFrEF) and mid-range ejection fraction (HFmrEF) using the TriNetX Research Network.•The primary composite outcome of hospitalizations and all-cause mortality demonstrated significant benefits with succinate in HFmrEF patients (28.6% vs 34.4%, p=0.018) and favorable trends in HFrEF patients (31.5% vs 35.2%, p=0.127).•Metoprolol succinate was associated with significantly improved event-free survival compared to tartrate in both HFrEF (64.12% vs 51.22%, p<0.001) and HFmrEF (67.57% vs 56.04%, p<0.001) populations in time-to-event analyses.•Extended-release pharmacokinetics of metoprolol succinate may provide more consistent β1-receptor blockade, supporting current guideline recommendations favoring succinate over tartrate. Despite widespread use of metoprolol formulations in heart failure (HF), direct comparative evidence of their clinical outcomes remains limited. 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. 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. 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. Visual Abstract. Propensity-matched analysis of metoprolol formulations in heart failure patients from the TriNetX Research Network. Metoprolol succinate demonstrated superior one-year event-free survival compared to tartrate for the primary composite outcome of hospitalizations and mortality in both HFrEF (64.12% vs 51.22%, p<0.001) and HFmrEF (67.57% vs 56.04%, p<0.001) populations, supporting current guideline recommendations for extended-release formulations. [Display omitted]
 Heart Failure Pharmacokinetics Metoprolol formulation Mortality

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