Roxadustat does not increase the rates of major adverse cardiovascular events (MACE) among patients with anemia of dialysis- or nondialysis-dependent chronic kidney disease (CKD), according to 2 late-breaking poster presentations at Kidney Week 2020 Reimagined, a virtual meeting of the American Society of Nephrology.
In both the dialysis and nondialysis trials, roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), corrected and/or maintained hemoglobin (Hb) levels at 11 g/dL during weeks 28-52.
In 2 pooled analyses, the rates of MACE (all-cause mortality, myocardial infarction, and stroke) and MACE+ (MACE plus heart failure and unstable angina requiring hospitalization) decreased with each successive Hb category.
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Among patients receiving dialysis, MACE and MACE+ generally decreased from 59.4 and 65.7 per 100 person-years, respectively, at Hb less than 8 g/dL to 7.2 and 9.8 per 100 person-years, respectively, at Hb 12 g/dL or higher, using the Hb level right before the event to define the categories, Robert Provenzano, MD, associate professor of medicine at Wayne State University in Detroit, Michigan, reported on behalf of his team. Results were similar using the maximum Hb level achieved over 12 weeks of treatment to define Hb categories. MACE and MACE+ rates decreased from 73.4 and 85.7 per 100 person-years, respectively, at Hb less than 8 g/dL to 10.1 and 11.9 per 100 person-years, respectively, at Hb 12 g/dL or higher.
Investigators found similar results in the nondialysis trials. MACE and MACE+ rates decreased from 60.9 and 82.9 per 100 person-years, respectively, at Hb less than 8 g/dL to 4.9 and 6.8 per 100 person-years, respectively, at Hb 12 g/dL or higher, using the Hb level right before the event to define the categories, Steven Fishbane, MD, of Northwell Health in Great Neck, New York, reported for his team. Using maximum achieved Hb, MACE and MACE+ rates were 97.9 and 97.9 per 100 person-years, respectively, at Hb less than 8 g/dL and 7.1 and 9.0 per 100 person-years, respectively, at Hb 12 g/dL or higher.
The lowest cardiovascular event rates were observed when Hb levels were 10 g/dL or higher, Dr Provenzano and Dr Fishbane reported.
The dialysis trials – ROCKIES, SIERRAS, and HIMALAYAS – included 1943 roxadustat-treated patients with dialysis-dependent CKD who had lower than normal mean Hb at baseline.
The nondialysis CKD trials – OLYMPUS, ANDES, and ALPS – involved 2391 roxadustat-treated patients with nondialysis-dependent CKD who had baseline Hb of 10 g/dL or less.
Neither the dialysis nor nondialysis trials were powered to examine the individual components of MACE and MACE+. However, in a third poster presentation, Dr Provenzano and colleagues took a closer look at heart failure hospitalization rates among recipients of roxadustat. Patients with dialysis-dependent CKD taking roxadustat had a significant 27% reduction in the risk for heart failure hospitalization compared with those using epoetin. Roxadustat-treated patients not receiving dialysis had a nonsignificant 11% reduced risk for the outcome compared with placebo recipients.
Disclosure: These clinical trials were supported by Fibrogen. Please see the original references for a full list of authors’ disclosures.
References
Provenzano R, Fishbane S, Pergola PE, et al. Associations between achieved hemoglobin and cardiovascular outcomes in the pooled phase 3 roxadustat studies of dialysis-dependent patients with anemia of CKD. Presented at: Kidney Week 2020 Reimagined; October 19-25, 2020. Poster PO2626.
Fishbane S, Provenzano R, Pergola PE, et al. Associations between achieved hemoglobin and cardiovascular outcomes in the pooled phase 3 roxadustat studies of non-dialysis-dependent patients with anemia of CKD. Presented at: Kidney Week 2020 Reimagined; October 19-25, 2020. Poster PO2625.
Provenzano R, Szczech L, Zhong M, et al. Pooled analyses of the phase 3 roxadustat studies: congestive heart failure hospitalization rates in dialysis and non-dialysis patients with anemia treated with roxadustat vs comparators. Presented at: Kidney Week 2020 Reimagined; October 19-25, 2020. Oral presentation SA-OR39.
