Iron supplementation for deficiency in acute HF lowers risk for future hospitalization
Click Here to Manage Email Alerts
Supplementation in iron-deficient patients hospitalized with acute HF reduced subsequent HF hospitalization by approximately 26% compared with placebo, according to findings from the AFFIRM-AHF trial.
Moreover, supplementation with IV ferric carboxymaltose (Vifor Pharma) did not appear to affect CV mortality in this population, according to research presented at the virtual American Heart Association Scientific Sessions.
“Iron deficiency is common in patients with heart failure, being accompanied by exercise intolerance, poor quality of life, increased risk for hospitalization and high morbidity and mortality,” Piotr Ponikowski, MD, PhD, head of the department of heart diseases at Wroclaw Medical University in Wroclaw, Poland, said at a press conference. “Correction of iron deficiency [improves these] symptoms... but the effects of ferric carboxymaltose administered at hospital discharged in stabilized patients with acute heart failure and concomitant iron deficiency [are] unknown and this issue remains extremely important as hospitalizations due to acute heart failure represent a growing health care problem [and] iron deficiency is present in up to 75% of these patients.”
For this trial, simultaneously published in The Lancet, investigators enrolled 1,108 patients hospitalized with acute HF and an iron deficiency. After stabilization, participants were randomly assigned to receive IV ferric carboxymaltose or placebo at discharge and at 6 weeks and were followed for 52 weeks to determine the effect of iron supplementation on subsequent HF hospitalization and CV death.
Patients whose iron deficiency persisted received re-administration of IV ferric carboxymaltose at weeks 12 and 24.
At 52 weeks, there was a lower prevalence of total HF hospitalizations and CV death among the ferric carboxymaltose group compared with the placebo group (RR = 0.79; 95% CI, 0.62-1.01) that was primarily driven by reduction in HF hospitalization (RR for HF hospitalization = 0.74; 0.58-0.94; HR for CV death = 0.96; 955 CI, 0.7-1.32).
“In patients with iron deficiency stabilized after an episode of acute heart failure, treatment with ferric carboxymaltose reduced the risk of heart failure hospitalization with no apparent effect on the risk of cardiovascular death,” Ponikowski said during a press conference. “In this high-risk population, ferric carboxymaltose reduced the total number of heart failure hospitalizations irrespective of anemia status.”
Researchers also observed reduced risk for first HF hospitalization or CV death among patients who received iron supplementation (HR = 0.8; 95% CI, 0.66-0.98) in addition to lower prevalence of total CV hospitalizations and CV death (RR = 0.8; 95% CI, 0.64-1).
“The management and follow-up of patients was affected by the COVID-19 pandemic, and as we all know, it impacted health care services provided and had potential consequences on heart failure epidemiology being acknowledged as a serious and unpredictable threat to the conduct of clinical trials,” Ponikowski said during the press conference. “Based on the recommendations of the European Society of Cardiology, European Medicines Agency and U.S. Food and Drug Administration, the statistical analysis plan included a pre-COVID-19 sensitivity analysis, censoring patients in each country at the day when its first COVID-19 patient was reported.”
This prespecified sensitivity analysis identified the following statistically significant differences in favor of IV ferric carboxymaltose supplementation before the onset of COVID-19 in a patient’s country:
- total HF hospitalizations and CV death (RR = 0.75; 95% CI, 0.59-0.96);
- total HF hospitalizations (RR = 0.7; 95% CI, 0.55-0.9);
- first HF hospitalization or CV death (HR = 0.79; 95% CI, 0.65-0.97);
- total CV hospitalizations and CV death (RR = 0.77; 95% CI, 0.62-0.97).
In the sensitivity analysis, there was no difference between the groups in CV death (HR = 0.94; 95% CI, 0.68-1.29).
Discussant Nancy K. Sweitzer, MD, PhD, professor of medicine, chief of cardiovascular medicine and director at the Sarver Heart Center University of Arizona in Tucson and Editor-in-Chief, Circulation: Heart Failure, said during the press conference that the trial “is likely to change practice in acute heart failure. Chronic iron deficiency is one of the most common comorbidities found in heart failure patients and arguably the most common comorbidity in our acute heart failure population that was studied in this trial. In addition to the well-known and recognized effect of iron to improve oxygen carrying capacity in our patients, independent of anemia, iron deficiency also impairs cellular energetics and immune function in patients, both of which may be very important in this population.
“Since we really do not think that iron is involved in the pathophysiology of established chronic heart failure with low ejection fraction or acute heart failure with low ejection fraction, it makes sense that this would have an impact on a quality-of-life endpoint and a patient related outcome rather than on death itself,” Sweitzer said. “This is an incredibly important endpoint for our patients and for the population studied in this trial.”
Reference:
Perspective
Back to Top
Paul J. Mather, MD, FACC, FACP, FAHA, FHFSA, FESC
The most important aspect of this trial is that iron deficiency is an important comorbid condition in acute HF and treatment with iron supplementation has reduced the risk for HF hospitalizations. Unfortunately, it hasn't saved lives. It does not have an impact on CV death risk. But we all know that downstream effects of being in the hospital can create morbidity and mortality. So that's an important point. Even though we do not have the CV risk benefit, we have a morbidity benefit.
Iron supplementation adds another co-factor to support making sure people are not anemic. Reducing the number of total HF hospitalizations is a very important thing and in the AFFIRM-AHF trial, patients’ anemic status did not correlate with it. You did not have to be anemic to benefit from reduction in total hospitalizations.
But more research is needed. Eighty percent of the patients required only one or two injections, but that means 20% needed more.
There was a statistically significant treatment benefit for an anti-anemia treatment in patients with HF for the first time. In the RED-HF trial and trials of other anemia drugs, we did not see benefit in patients with HF.
Also important is that the treatment was safe.
HF is not a disease entity. It is more of an "all roads lead to Rome" disease process; many things can impact on it. Each one of those have to be addressed. Everything from anemia to nutrition, mental well-being, compliance, access to health care, social determinants of health, food deserts and trust in the institutional health care system impact outcomes in HF, which is a comorbid condition of multiple factors.
Collapse
Ponikowski P, et al. Heart failure and atrial fibrillation: Vitamins, minerals, nutrients, and more. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
Click Here to Manage Email Alerts