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Kidney Week

Abstract: FR-OR133

The Dapagliflozin in Heart Failure with Reduced Ejection Fraction Trial (DAPA-HF): Outcomes in Patients with CKD and Effects on Renal Function

Session Information

  • High-Impact Clinical Trials
    November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 02:30 PM - 02:45 PM

Category: CKD (Non-Dialysis)

Authors

  • Solomon, Scott D., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jhund, Pardeep, BHF Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom
  • Kosiborod, Mikhail, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, United States
  • Verma, Subodh, St. Michael's Hospital, Toronto, Ontario, Canada
  • Inzucchi, Silvio E., Yale University School of Medicine, New Haven, Connecticut, United States
  • Langkilde, Anna Maria, AstraZeneca , Gothenburg, Sweden
  • Martinez, Felipe, DAMIC Institute, Cordoba, Argentina
  • Bengtsson, Olof, Astrazeneca, Molndal, Sweden
  • Docherty, Kieran F, BHF Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom
  • Køber, Lars, Rigshospitalet, Copenhagen, Denmark
  • Sjostrand, Mikaela, Astrazeneca, Molndal, Sweden
  • Sabatine, Marc S., TIMI Study Group, Boston, Massachusetts, United States
  • McMurray, John, University of Glasgow, Glasgow, United Kingdom

Group or Team Name

  • DAPA-HF Executive Committee
Background

A substantial proportion of patients with heart failure and reduced ejection fraction (HFrEF) have or develop chronic kidney disease (CKD). SGLT-2 inhibitors have been shown to delay the progression of kidney disease and reduce the incidence of cardiac events in patients with type 2 diabetes (T2D) and CKD. Dapagliflozin (DAPA) was shown in the DAPA-HF Trial to reduce the primary composite outcome of a worsening heart failure event or cardiovascular death in patients with HFrEF, both with and without T2D

Methods

We randomized 4744 patients with NYHA class II-IV heart failure, LVEF ≦40%, elevation in natriuretic peptides and optimal background HFrEF therapy to DAPA 10mg qd or placebo (PBO). The primary outcome is described above. The prespecified secondary renal outcome was a sustained ≥50% reduction in eGFR, end-stage renal disease or death from renal causes. We also prespecified an analysis of the effect of DAPA, compared to PBO, in patients with and without CKD (eGFR <60 ml/min/1.73m2 at baseline).

Results

Overall, 45% of patients had T2D and 55% did not. The baseline eGFR was 65.8 ± 19.4 ml/min/1.73m2 and 1926 (40.6%) patients had CKD. A worsening heart failure event or cardiovascular death (the primary end point) occurred in 386 patients (16.3%) in the DAPA group and 502 patients (21.2%) in the PBO group: hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.65-0.85; P<0.001. DAPA reduced the primary outcome by a similar magnitude in patients with CKD (HR 0.72, 95%CI 0.59-0.86) and without CKD (HR 0.76, 95%CI 0.63, 0.92) - results to be shown at ASN. The composite renal endpoint was observed in 28 (1.2%) patients in the DAPA group vs 39 (1.6%) in the PBO arm (HR 0.71, 95% CI 0.44, 1.16). Renal serious adverse events and investigator reported acute kidney injury were significantly less common in the DAPA group. Additional results, including eGFR over-time, will be shown at the ASN annual meeting.

Conclusion

In this trial including HFrEF patients with and without T2D, DAPA reduced the composite of a worsening heart failure event or cardiovascular death, both in participants with CKD and in those without CKD. The absolute benefit in patients with CKD was substantial.

Funding

  • Commercial Support