Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

Jawad H Butt; Pardeep S Jhund; Kieran F Docherty; Brian L Claggett; Muthiah Vaduganathan; Erasmus Bachus; Adrian F Hernandez; Carolyn S P Lam; Silvio E Inzucchi; Felipe A Martinez; Rudolf A de Boer; Mikhail N Kosiborod; Akshay S Desai; Lars Køber; Piotr Ponikowski; Marc S Sabatine; Scott D Solomon; John J V McMurray

doi:10.1016/j.jchf.2024.01.018

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

JACC Heart Fail. 2024 Mar 22:S2213-1779(24)00149-5. doi: 10.1016/j.jchf.2024.01.018. Online ahead of print.

Authors

Jawad H Butt¹, Pardeep S Jhund², Kieran F Docherty², Brian L Claggett³, Muthiah Vaduganathan³, Erasmus Bachus⁴, Adrian F Hernandez⁵, Carolyn S P Lam⁶, Silvio E Inzucchi⁷, Felipe A Martinez⁸, Rudolf A de Boer⁹, Mikhail N Kosiborod¹⁰, Akshay S Desai³, Lars Køber¹¹, Piotr Ponikowski¹², Marc S Sabatine¹³, Scott D Solomon³, John J V McMurray¹⁴

Affiliations

¹ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
² British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
³ Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R and D, AstraZeneca, Gothenburg, Sweden.
⁵ Duke University Medical Center, Durham, North Carolina, USA.
⁶ National Heart Centre Singapore, Singapore.
⁷ Duke-National University of Singapore, Singapore; Yale School of Medicine, New Haven, Connecticut, USA.
⁸ University of Cordoba, Cordoba, Argentina.
⁹ Erasmus Medical Center, Rotterdam, Netherlands.
¹⁰ Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA.
¹¹ Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
¹² Department of Heart Disease, Wroclaw Medical University, Wroclaw, Poland.
¹³ TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁴ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.mcmurray@glasgow.ac.uk.

PMID: 38573262
DOI: 10.1016/j.jchf.2024.01.018

Abstract

Background: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."

Objectives: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).

Methods: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.

Results: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; P_interaction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.

Conclusions: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Keywords: clinical trial; heart failure; outcomes.