Kidney Week

Abstract: TH-PO902

Major Adverse Cardiovascular Events (MACE) in Patients Randomly Assigned to Vadadustat vs. Darbepoetin Alfa during the 3 Months after Dialysis Initiation

Session Information

• Anemia and Iron Metabolism
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Winkelmayer, Wolfgang C., Baylor College of Medicine, Houston, Texas, United States

Wolfgang C. Winkelmayer, MD, ScD, MPH, FASN

• Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Steven K. Burke, MD

• Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany

Kai-Uwe Eckardt, MD

• Lewis, Eldrin F., Stanford University School of Medicine, Stanford, California, United States

Eldrin F. Lewis, MD

• Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Wenli Luo, MD, PhD

• Minga, Todd Eric, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Todd Eric Minga, MD

• Sarnak, Mark J., Tufts University School of Medicine, Boston, Massachusetts, United States

Mark J. Sarnak, MD, MS

Background

Trials and registries usually do not capture events during the weeks following dialysis initiation, when cardiovascular event rates and mortality are particularly high. The PRO₂TECT trials compared vadadustat (VADA), an oral HIF-PHI, and the ESA darbepoetin alfa (DA), in patients with non–dialysis-dependent (NDD)-CKD (ESA-untreated [NCT02648347] and ESA-treated [NCT02680574]). Many PRO₂TECT patients progressed to kidney failure and initiated dialysis, thus providing an opportunity to study this vulnerable incident dialysis period.

Methods

The PRO₂TECT Ph 3 trials randomized 3476 patients with anemia and NDD-CKD 1:1 to VADA or DA. This post-hoc analysis anchored baseline at dialysis initiation and followed patients for up to 90 days. We estimated cumulative incidences and rate ratios (RR) with 95% confidence intervals (CI) of MACE (all-cause mortality, nonfatal MI, nonfatal stroke) and expanded MACE (MACE plus hospitalizations for either heart failure or a thromboembolic event). We also described event rates in 30-day intervals for 90 days after dialysis initiation.

Results

527 patients randomized to VADA and 539 patients randomized to DA initiated dialysis. The median [25^th, 75^th percentile] time since trial enrolment was 255 [122, 448] days in the VADA and 268 [142, 483] days in the DA group. In the first 90 days after dialysis initiation, 50 patients (9.5%) in the VADA group and 55 patients (10.2%) in the DA group had a MACE (RR=0.93; 95% CI: 0.65-1.34]). During the same time, 57 patients (10.8%) in the VADA group and 67 patients (12.4%) in the DA group had an expanded MACE (RR=0.87; 95% CI, 0.62-1.21). Incidence of expanded MACE was highest in the 30 days after dialysis initiation (Table), where most events were deaths.

Conclusion

Rates of MACE and expanded MACE within the first 90 days of dialysis initiation were similar among patients randomized to VADA vs. DA. The majority of these events occurred in the first 30 days after dialysis initiation.

Expanded MACE After Dialysis Initiation

Funding

• Commercial Support – Akebia Therapeutics, Inc.