Abstract Body (Do not enter title and authors here): Background: In PARAGLIDE-HF, patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) and a recent worsening HF event randomized to sacubitril/valsartan (sac/val) vs val had a significantly larger reduction in NT-proBNP and were numerically more likely to derive clinical benefit as assessed by a win ratio. Patients with obesity and HFpEF may represent a unique phenotype, characterized by a high risk for recurrent HF hospitalization and lower levels of NT-proBNP.

Research Question: Does BMI category modify the relationship between sac/val vs val on NT-proBNP change and/or a win ratio among patients with HFpEF or mildly reduced EF?

Methods: To assess the interaction between BMI and sac/val vs val on NT-proBNP, the time-averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8 was assessed with an analysis of covariance model including the interaction of treatment-by-BMI group (obese with BMI ≥30 vs normal/overweight, BMI 18.5 to <30 kg/m²). A win ratio of cardiovascular death, total HF hospitalizations, urgent HF visits, and change in NT-proBNP was calculated for both BMI groups, including an interaction term with significance set at ≤0.1.

Results: Overall, 65% (n=298) of patients had obesity and 35% (n=164) of patients had normal/overweight. When the interaction between BMI category and the effect of sac/val vs val on the time-averaged proportional change from baseline NT-proBNP was assessed, patients with obesity had a non-significant but numerically larger decrease in NT-proBNP (Table). Patients with obesity were also more likely to derive clinical benefit overall from sac/val vs val as compared to patients with normal/overweight (win ratio 1.38, 95% CI 1.01-1.90 vs 0.90, 95% CI 0.62-1.32, p interaction = 0.09).

Conclusion: These preliminary data suggest that patients with HF with mildly reduced or preserved EF and obesity may experience a larger clinical benefit from sac/val than patients with normal/overweight BMI.