IV iron cuts risk of HF rehospitalization, CV death in ambulatory HFrEF patients
In a broad range of patients with HFrEF* and iron deficiency, the administration of IV ferric derisomaltose (FDI) was associated with a lower risk of recurrent hospitalization for heart failure (HHF) and cardiovascular (CV) death compared with standard of care (SoC), findings from the IRONMAN** trial have shown.
The rate of the primary composite outcome was lower with IV FDI than with SoC (22.4 vs 27.5 per 100 patient-years [PY]), translating to an 18-percent risk reduction (relative risk [RR], 0.82; p=0.07). [AHA 2022, Late-Breaking Science Session LBS.02]
Key secondary endpoints showed trends favouring IV FDI over SoC (16.7 vs 20.9/100 PY; RR, 0.80; p=0.08 [HHF] and 21 percent vs 24 percent; hazard ratio [HR], 0.86; p=0.23 [CV death]).
Individuals on IV FDI had significantly better quality of life (QoL) than those receiving SoC based on the MLHFQ*** at 4 months (36.9 vs 40.2; estimated treatment effect, –3.33; p=0.05). However, the effect waned by month 20 (40.1 vs 42.7; estimated treatment effect, –2.57; p=0.23).
COVID-19 sensitivity analysis: Statistical significance met
“In a trial that was markedly impacted by the COVID-19 pandemic, in the prespecified analysis evaluating 91 percent of the total cohort, there was a 24-percent significant reduction in the risk of the primary endpoint (RR, 0.76; p=0.047),” said chief study investigator Dr Paul Kalra from the Portsmouth Hospitals University NHS Trust and University of Glasgow, UK, at AHA 2022.
The secondary outcomes followed a trend similar to that seen in the main analysis (RR, 0.76; p=0.08 [HHF] and HR, 0.79; p=0.15 [CV death]).
The risk reductions were lower on post hoc sensitivity analysis at 1 year, both in terms of the primary (RR, 0.66; p=0.01) and secondary endpoints (RR, 0.66; p=0.02 [HHF] and HR, 0.67; p=0.09 [CV death]). “I think these data combined do help demonstrate the impact the COVID-19 pandemic had on our trial,” noted Kalra.
Practice guidelines may evolve
Kalra and colleagues randomized 1,137 nonhospitalized individuals (median age 74 years, 73 percent male) 1:1 to receive IV FDI or SoC. They were reviewed every 4 months thereafter. Iron was re-administered if serum ferritin was <100 µg/L or TSAT# was <25 percent. Median follow-up was 2.7 years.
There was no signal of excess risk of infection with FDI compared with SoC for either hospitalization (11.7 vs 14.2) or death (6 percent vs 5 percent). Looking at serious adverse events (AEs), there was no signal of excess harm. “In fact, there were statistically fewer cardiac events with FDI vs SoC (36 percent vs 43 percent; p=0.016),” noted Kalra.
“IRONMAN adds substantially to our knowledge of the efficacy and safety of IV iron for patients with HF, with no evidence of an excess of AEs,” said Kalra. “These results are likely to influence clinical practice and guidelines in Europe and North America.”
“In Europe, guidelines are specific to ferric carboxymaltose alone … In the US, we relegate IV iron to improve functional capacity as a comorbidity and HF … [Given the similarities between AFFIRM and IRONMAN], perhaps these guidelines will expand,” said discussant Dr Gregory Lewis from the Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, US, at AHA 2022.
“Two different preparations [of IV iron] now numerically show reduction in HHF and CV death by ~20 percent, driven by a reduction in HHF. We eagerly await the [results of the] HEART-FID trial, which will provide a threefold higher sample size and may corroborate the outcomes that we just saw,” added Lewis.
Addresses a common comorbidity in HF
“IRONMAN was a very important study because it addresses something very common in HF – iron deficiency – which is present in almost half of our patients … This is not just anaemia,” commented Dr Carolyn Lam from the National Heart Centre, Singapore, at AHAtv following the presentation.
“IRONMAN investigators must be praised for their commitment to a major unmet question of HF treatment, long-term efficacy, and safety of iron deficiency correction, paving the way for better treatment of our patients,” said Professor Marco Metra from University of Brescia, Italy, at ESC TV On the Road, which delivered insightful opinions on studies presented at AHA 2022.