MO531: The Differential Effect of Third-Generation Intravenous Iron Preparations (Ferric Carboxymaltose, Ferric Derisomaltose) on Cardiovascular Parameters in Patients With Non-Dialysis Dependent CKD and Iron Deficiency Anaemia
Authors: Kassianides Xenophon , Bhandari Sunil 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Intravenous (IV) iron is commonly used to alleviate iron deficiency anaemia in patients with non-dialysis chronic kidney disease (CKD). Treatment with IV iron in patients with iron deficiency and heart failure has demonstrated an improvement in functional status and cardiac biomarkers; however, concerns remain regarding the potential pro-oxidative effect of IV iron and possible cardiovascular injury. Newer agents [such as ferric carboxymaltose (FCM) and ferric derisomaltose (FDI)] are increasingly used due to their advantage in delivering large amounts of iron effectively and safely; however, they differ as to their effect on serum phosphate and fibroblast growth factor 23, factors that have been previously shown to affect cardiac function. Given the above potential concerns, it is important to explore the comparative effect of IV iron in this population in terms of cardiac injury and vascular function.

METHOD
The exploratory single-centre double-blinded randomized controlled trial ‘Iron and Phosphaturia—ExplorIRON-CKD’ aimed primarily to not only assess the differential effects of FCM and FDI on levels of fibroblast growth factor 23 and phosphate, but also explore any cardiovascular effect. Non-dialysis patients with CKD and iron deficiency with/without anaemia defined as serum ferritin &lt;200 µg/L or transferrin saturation ≤20% and serum ferritin 200–299 µg/L were recruited and randomized in a 1:1 ratio. Participants received 1000 mg at baseline and 500–1000 mg at 1 month to achieve replenishment. Measurements of NT-proBNP were taken at baseline, 1 month, 2 months and 3 months, whilst measurements of Troponin T were taken at every visit (total of eight visits). Vascular function was assessed using pulse wave velocity measurements at baseline, 1 month, 2 months and 3 months, monitoring carotid to femoral pulse wave velocity (PWVcf) and aortic augmentation index (AIx).

RESULTS
Twenty-six patients were recruited; 14 were randomized to receive FDI and 12 to receive FCM. All patients received at least one iron dose (1000 mg), 10 patients received two FDI doses and 11 received two FCM doses. There was a trend to an increase in NT-pro BNP (10.3%) in the combined group, with no statistical difference between the FCM and FDI groups [median for the combined population: baseline: 875.5 (3033.0) ng/L versus Visit 8: 967.0 (2976.0) ng/L] (Figure 1). Troponin T values remained constant throughout the study period in the combined and individual groups (Table 1). A decrease in both PWVcf and AIx was noted in the participants receiving IV iron irrespective of the compound used. A greater decrease was seen in the FDI group in terms of PWVcf; however, there was no statistically significant difference for the percentage change from baseline to the end of the study between the groups (FCM: −4.3 (33.6)% versus FDI: −11.9 (23.4)%; P = .60) (Figure 2).

CONCLUSION
Treatment of non-dialysis CKD patients with FDI or FCM was not associated with any cardiovascular safety signals. Troponin T was unaffected and there was no worsening in vascular function. Pulse wave velocity improved, as noted by the decreasing trends for PWVcf and AIx. The decrease in PWVcf was greater with FDI than FCM, but the difference was not statistically significant. A small rise in NT-proBNP was noted in the combined group, but there was no statistically significant difference between the FDI and FCM groups. These results suggest that newer IV iron compounds are not associated with any detriment in terms of vascular function and potentially no resulting cardiac insult. The study sample is small and therefore the results should be interpreted with caution; nonetheless, the evidence provided from a comparative view directs to no negative sequela.