Adv Ther. 2022 Aug 10. doi: 10.1007/s12325-022-02242-x. Online ahead of print.

Richard F Pollock ¹, Philip A Kalra ², Paul R Kalra ^3 4, Fozia Z Ahmed ^5 6

Author information

¹Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD, UK. pollock@covalence-research.com.

²Department of Renal Medicine, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK.

³Department of Cardiology, Portsmouth Hospitals University NHS Trust, Portsmouth, UK.

⁴Faculty of Science and Health, University of Portsmouth, Portsmouth, UK.

⁵Department of Cardiology, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.

⁶Manchester University NHS Foundation Trust, Manchester, UK.

Abstract

Introduction: Intravenous (IV) iron is the preferred treatment for patients with iron deficiency anemia (IDA) who require rapid replenishment of iron stores or in whom oral iron is not tolerated or effective. Data from two large-scale randomized controlled trials (RCTs) have recently been published reporting the incidence of adjudicated cardiovascular events after ferric derisomaltose (FDI) and iron sucrose (IS). The objective was to calculate the relative incidence of cardiovascular events with FDI and IS, and to conduct an indirect comparison with ferric carboxymaltose (FCM) based on previously published studies of cardiovascular risk.

Methods: RCTs reporting the incidence of blindly adjudicated cardiovascular events in IDA patients treated with IV iron were identified by systematic literature review (SLR). Pairwise random effects meta-analyses of FDI versus IS, and FCM versus IS were conducted for the pre-specified adjudicated composite cardiovascular endpoint of: death due to any cause, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmia, and protocol-defined hypertensive and hypotensive events. Analyses were also conducted for the composite endpoint excluding blood pressure events. Meta-analysis results were combined in an adjusted indirect comparison to provide an indirect estimate of cardiovascular risk with FDI versus FCM.

Results: The SLR retrieved 694 unique articles, of which four were RCTs reporting the incidence of the composite cardiovascular endpoint; two studies comparing FCM (N = 1529) with IS (N = 1505), and two studies comparing FDI (N = 2008) with IS (N = 1000). The odds ratios of the composite CV endpoint were 0.59 (95% confidence interval: 0.39-0.90) for FDI versus IS, 1.12 (95% CI 0.90-1.40) for FCM versus IS, and the indirect OR for FDI versus FCM was 0.53 (95% CI 0.33-0.85).

Conclusions: Pooling data from four large-scale RCTs suggested that FDI was associated with significantly lower incidence of cardiovascular adverse events compared to both FCM and IS.