A new post hoc analysis of the SUMMIT trial suggests the HFpEF-ABA score is a more effective and inclusive enrichment tool than natriuretic peptide (NP) levels for clinical trials in patients with obesity-related heart failure with preserved ejection fraction (HFpEF).¹ The findings indicate the score, which is based on age, body mass index (BMI), and history of atrial fibrillation (AF), can identify high-risk patients who are often excluded by traditional NP-based criteria.
This analysis utilised data from the SUMMIT trial, a randomised, placebo-controlled study evaluating tirzepatide in patients with obesity-related HFpEF (ejection fraction ≥50%, BMI ≥30 kg/m²).² The co-primary endpoints were the time to first adjudicated cardiovascular death or worsening HF, and the change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 52 weeks.
For this analysis, 731 participants were categorised into three groups based on their baseline HFpEF-ABA score probability: <75% (n=219), 75–89% (n=215), and ≥90% (n=297). Researchers evaluated baseline characteristics, risk for the primary endpoint, and treatment response across these groups.
A higher HFpEF-ABA score was associated with greater disease severity across multiple domains, including a higher prevalence of NYHA class III-IV symptoms, lower KCCQ-CSS scores, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (p<0.001 for all).
In the placebo arm, the risk of cardiovascular death or worsening HF increased markedly with higher HFpEF-ABA scores. Event rates were 3.15, 7.50, and 15.37 per 100 patient-years for the low, intermediate, and high-score groups, respectively (p<0.001).
The relative risk reduction with tirzepatide was consistent across all score categories (p for trend=0.76). However, due to the higher baseline event rates, the absolute risk reduction was numerically greater in patients with higher scores, with a reduction of 5.74 per 100 person-years in the ≥90% score group.
Notably, only 26.7% of the SUMMIT trial population would have met the NT-proBNP eligibility criteria used in other contemporary HFpEF trials. This suggests that relying on NP levels would have excluded over 70% of high-risk patients who demonstrated benefit from the intervention.
These results highlight the limitations of using NT-proBNP levels for patient selection in HFpEF trials, particularly in the context of obesity where levels can be paradoxically lower. The HFpEF-ABA score provides a simple, NP-agnostic method to identify patients at high risk for adverse events. Adopting this score as an enrichment criterion could enhance trial enrolment and ensure results are more generalisable to the broader HFpEF community.
The authors note that while these findings are promising for patients with obesity-related HFpEF, further validation in independent cohorts and in patients with a lower BMI is warranted.
This study was funded by Eli Lilly and Company.
References
1. Borlaug BA, Zile MR, Kramer CM, et al. HFpEF-ABA score is a more useful enrichment tool than natriuretic peptides in heart failure with preserved ejection fraction. Eur Heart J 2025;46(43):4607–4609. https://doi.org/10.1093/eurheartj/ehaf663
2. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2025;392:427–37. https://doi.org/10.1056/NEJMoa2410027
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