1832-P: Emulation of a Trial of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER)

Introduction and Objective: Non-randomized studies may advance understanding of treatment effectiveness in heart failure (HF) and type 2 diabetes (T2D), but whether they can replicate outcomes comparable with clinical trials is uncertain. Methods: In this new-user, active-comparator cohort study using 3 US claims databases from 2014-2021 (pre-DELIVER publication [2022]), we identified 1:1 propensity score (PS)-matched adults aged ≥40 years initiating dapagliflozin or sitagliptin (observational placebo proxy) who had HFmrEF/HFpEF and T2D, and met key DELIVER trial eligibility criteria. The primary outcome was a composite of all-cause mortality (ACM) or HF hospitalization (HFH). Results: Key baseline characteristics were comparable between the routine care (n=8,162) and DELIVER (n=2,806) populations (Table). Among 1:1 PS-matched US adults with HFmrEF/HFpEF and T2D, dapagliflozin was associated with a 24% lower rate of ACM or HFH vs. sitagliptin (HR, 0.76; 95% CI, 0.63-0.92) (Table). Findings were consistent with the effect of dapagliflozin on the exploratory endpoint of ACM or HFH in DELIVER (HR, 0.84; 95% CI, 0.73-0.97) (Table). Similar concordance was observed for the primary outcome components. Conclusion: The directional consistency of these findings highlights the potential of rigorous non-randomized studies using fit-for-use data to advance understanding of the effectiveness of HF treatments in T2D. Disclosure J. Ostrominski: Advisory Panel; Current; Corcept Therapeutics. C. Byrne: None. S.D. Solomon: Research Support; Current; Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cardior, Cytokinetics, Edgewise, BridgeBio, Gossamer, GSK, Ionis, Lilly, NIH/NHLBI, Novartis, NovoNordis. Consultant; Current; Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, Askbio, AstraZeneca, Bayer, BMS, Bridgebio, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantu. O. Vardeny: Research Support; Current; AstraZeneca, Bayer AG, Cardurion. Consultant; Ended; Cardior. Consultant; Current; Cytokinetics Inc. J. Ortega-Montiel: None. J. Paik: None. M. Bradley: None. E. Patorno: Research Support; Current; Boehringer Ingelheim International GmbH, AstraZeneca, Bayer AG, National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute. Other - Royalties; Current; UpToDate.