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<p>Comparative effectiveness evidence between mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved ejection fraction (HFpEF) is limited, particularly under real-world conditions where drug selection is shaped by renal function, laboratory monitoring capacity, and health-system constraints. The recent federated electronic health record–based analysis comparing finerenone with spironolactone provides valuable hypothesis-generating insights into safety and mortality outcomes. However, the marked imbalance in exposure groups, potential residual confounding, and limited reporting of absolute risks and monitoring intensity restrict direct clinical transportability. In this correspondence, we highlight key decision-critical considerations related to cohort selectivity, background therapy interactions, potassium dynamics, and health-system heterogeneity, and propose pragmatic analytical and implementation refinements to strengthen causal interpretability and global applicability of future comparative studies in HFpEF.</p>

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From Hypothesis-generating to Decision-grade: Making Finerenone–spironolactone Comparisons in HFpEF Globally Implementable

  • 期刊论文

  • 发表日期：

    2026年3月9日

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  • M. Vijayasimha,
  • M. Srikanth,
  • Gurjeet Singh

摘要

Comparative effectiveness evidence between mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved ejection fraction (HFpEF) is limited, particularly under real-world conditions where drug selection is shaped by renal function, laboratory monitoring capacity, and health-system constraints. The recent federated electronic health record–based analysis comparing finerenone with spironolactone provides valuable hypothesis-generating insights into safety and mortality outcomes. However, the marked imbalance in exposure groups, potential residual confounding, and limited reporting of absolute risks and monitoring intensity restrict direct clinical transportability. In this correspondence, we highlight key decision-critical considerations related to cohort selectivity, background therapy interactions, potassium dynamics, and health-system heterogeneity, and propose pragmatic analytical and implementation refinements to strengthen causal interpretability and global applicability of future comparative studies in HFpEF.