Stroke in hemodialysis patients randomized to different intravenous iron strategies: a prespecified analysis from the PIVOTAL trial

Mark, P. B. et al. (2021) Stroke in hemodialysis patients randomized to different intravenous iron strategies: a prespecified analysis from the PIVOTAL trial. Kidney360, 2(11), pp. 1761-1769. (doi: 10.34067/KID.0004272021)

Abstract

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared to similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized controlled trial of intravenous iron treatment strategies in HD. Methods: We analyzed data from the Proactive IV IrOn Therapy in HaemodiALysis Patients (PIVOTAL) trial focusing on variables associated with risk of stroke. The trial randomized 2,141 adults, who had started hemodialysis <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA), to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke. Results: During a median 2.1 years follow-up, 69 (3.2%) patients experienced a first post randomization stroke. 57 (82.6%) were ischemic strokes and 12 (17.4%) hemorrhagic strokes. There were 34 post randomization strokes in the proactive arm and 35 in the reactive arm (hazard ratio (95% confidence interval): 0.90 (0.56, 1.44), p=0.66). In multivariable models, female gender, diabetes, history of prior stroke at baseline, higher baseline systolic blood pressure, lower serum albumin and higher C-reactive protein were independently associated with stroke events during follow up. Hemoglobin, total iron or ESA dose were not associated with risk of stroke. 58% of patients with a stroke event died during follow-up, compared to 23% without a stroke. Conclusions: In hemodialysis patients, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.

• Item Type: Articles
• Additional Information: The PIVOTAL trial was funded by Kidney Research UK which was supported by an unrestricted grant from Vifor Fresenius Medical Care Renal Pharma.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robertson, Mrs Michele and Walters, Professor Matthew and Jhund, Professor Pardeep and Mark, Professor Patrick and Petrie, Professor Mark and Ford, Professor Ian and McMurray, Professor John and Connolly, Dr Eugene
• Authors: Mark, P. B., Jhund, P. S., Walters, M. R., Petrie, M. C., Power, A., White, C., Robertson, M., Connolly, E., Anker, S. D., Bhandari, S., Farrington, K., Kalra, P. A., Tomson, C. R.V., Wheeler, D. C., Winearls, C. G., McMurray, J. J.V., Macdougall, I. C., and Ford, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Kidney360
• Publisher: American Society of Nephrology
• ISSN: 2641-7650
• ISSN (Online): 2641-7650
• Published Online: 16 September 2021
• Copyright Holders: Copyright © 2021 American Society of Nephrology
• First Published: First published in Kidney360 2(11): 1761-1769
• Publisher Policy: Reproduced in accordance with the publisher copyright policy