Renal and blood pressure effects of dapagliflozin in recently hospitalized patients with heart failure with mildly reduced or preserved ejection fraction: Insights from the DELIVER trial |
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| Authors: | Safia Chatur Jonathan W Cunningham Muthiah Vaduganathan Finnian R Mc Causland Brian L Claggett Akshay S Desai Zi Michael Miao Pardeep S Jhund Rudolf A de Boer Adrian F Hernandez Silvio E Inzucchi Mikhail N Kosiborod Carolyn SP Lam Felipe A Martinez Sanjiv J Shah Magnus Petersson Anna Maria Langkilde John JV McMurray Scott D Solomon |
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| Institution: | 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;2. Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;3. BHF Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health University of Glasgow, Glasgow, UK;4. Erasmus Medical Center, Department of Cardiology, Rotterdam, The Netherlands;5. Duke University Medical Center, Durham, NC, USA;6. Yale School of Medicine, New Haven, CT, USA;7. Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas, MO, USA;8. National Heart Centre Singapore & Duke-National University of Singapore, Singapore, Singapore;9. Universidad Nacional de Córdoba, Córdoba, Argentina;10. Northwestern University Feinberg School of Medicine, Chicago, IL, USA;11. Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden |
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| Abstract: | Aims Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized. Methods and results We examined the effects of dapagliflozin versus placebo on estimated glomerular filtration rate (eGFR) slope (acute and chronic), 1-month change in systolic blood pressure, and the occurrence of serious hypovolaemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization. The 654 (90 randomized during hospitalization, 147 1–7 days post-discharge and 417 8–30 days post-discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization (median interquartile range] 55 43, 71] vs. 60 47, 75] ml/min/1.73 m2). Dapagliflozin consistently reduced the risk of all-cause (pinteraction = 0.20), cardiac-related (pinteraction = 0.75), and HF-specific (pinteraction = 0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo-corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (?2.0 ?4.1, +0.1] vs. ?3.4 ?3.9, ?2.9] ml/min/1.73 m2, pinteraction = 0.12). Dapagliflozin's effect to slow chronic eGFR decline was similar regardless of recent hospitalization (pinteraction = 0.57). Dapagliflozin had a minimal effect on 1-month systolic blood pressure and to a similar degree in patients with and without recent hospitalization (?1.3 vs.?1.8 mmHg, pinteraction = 0.64). There was no treatment-related excess in renal or hypovolaemic serious adverse events, irrespective of recent HF hospitalization. Conclusion In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on blood pressure and did not increase renal or hypovolaemic serious adverse events, yet afforded long-term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF. Clinical Trial Registration: ClinicalTrials.gov NCT03619213. |
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| Keywords: | Acute heart failure SGLT2 inhibitor Renal function Blood pressure |
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