Announcer:
Welcome to CME on ReachMD. This activity, entitled “AHA 2020: New Insights on Iron Deficiency and Heart Failure” is provided by Medtelligence and is supported by an independent educational grant from Vifor Pharma.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the Learning Objectives.
Dr. Butler:
We know for a fact that about 50% of patients with heart failure are iron deficient. Iron deficiency is associated with poor exercise capacity, poor quality of life and increased mortality. Hospitalized patients with acute heart failure often have iron deficiency independent from anemia. Should we be treating iron deficiency in our patients who are hospitalized with heart failure?
This is CME on ReachMD. I am Dr. Javed Butler, and joining me for today’s discussion are Drs. Piotr Ponikowski and Gerasimos Filippatos.
Dr. Filippatos:
Hello, thank you very much for the invitation, Javed. Great pleasure being here.
Dr. Ponikowski:
Hello, Javed. Hello, Gerasimos. Thank you very much for the invitation. Thank you very much for having me here. Thank you for that opportunity to discuss AFFIRM-AHF study.
Dr. Butler:
Great to have you guys. So, Dr. Filippatos, based on what we know today, is iron deficiency a risk marker or a risk factor?
Dr. Filippatos:
I think, Javed, that iron deficiency is both a risk marker and a risk factor for heart failure patients. It is related to worse dyspnea class, worse exercise capacity and quality of life, and higher mortality and cardiac transplantation. And it is a risk factor because intravenous administration of iron, or ferric carboxymaltose, as it has been shown in several trials, including CONFIRM Heart Failure, FAIR Heart Failure, in the meta-analysis of patient-level data is associated with improvement of quality of life and cardiac function, increased exercise tolerance and maximal oxygen consumption, and it reduces hospitalization in patients with heart failure with reduced ejection fraction.
Dr. Butler:
So turning to you now, Dr. Ponikowski, we know that treatment with IV iron leads to good outcomes for patients with stable heart failure with reduced ejection fraction. You’re looking at a different population. Tell us about the goals of AFFIRM-AHF study. What was the question you and your colleagues were trying to answer?
Dr. Ponikowski:
Yes, Javed, indeed. Gerasimos just told us about stable patients with chronic heart failure, and we know that among patients who are acutely admitted due to heart failure decompensation, about 70%–80% have concomitant iron deficiency. We also know that this is independently linked with the outcome. We believe that intervening at this stage, once patients are stabilized, ready for going home, ready for discharge, IV iron repletion would change the outcome, would decrease the risk of hospital readmissions and cardiovascular death. It was the major idea behind the study. So patients who were acutely admitted with iron deficiency at the very risk of post-discharge rehospitalization or cardiovascular death, to intervene to replete iron before discharge and at the period post-discharge, which is, as we all know, the most vulnerable phase in the natural history in order to improve patients’ outcomes.
Dr. Butler:
Indeed. For those just tuning in, you are listening to CME on ReachMD. I am Dr. Javed Butler, and here with me today are Drs. Piotr Ponikowski and Gerasimos Filippatos. We are discussing new data that was released at the American Heart Association Scientific Session 2020 around the treatment of iron deficiency in acute heart failure.
So tell us, Dr. Ponikowski, what did you see when iron deficiency was corrected in patients who were hospitalized for acute heart failure?
Dr. Ponikowski:
First, let me tell you who participated in the study. As I said, we focused on patients who were hospitalized for acute heart failure. We wanted to make sure that we really had patients with acute heart failure, so the criterium was that this niche needed to be confirmed by signs and symptoms and elevated natriuretic peptides. The second inclusion criterion was iron deficiency as defined in the ESC [European Society of Cardiology] guidelines, ESC Heart Failure Guidelines. We also requested patients to have left ventricular ejection fraction below 50% documented within the recent 12 months before admission.
We had standard exclusion criteria, but I would like to reiterate that we excluded patients with active infection requiring anti-MAC microbial treatment during the indexed hospitalization. The primary endpoint of the study was a composite of total heart failure hospitalization and cardiovascular death until up to 52 weeks. This is pretty important because we focused on the recurrent events. We didn’t use only time to first event, but we focused on recurrent heart failure hospitalization, keeping in mind that this is really the burden of heart failure we want to interfere with.
There were 1,100 patients, 1,108 patients finally studied, equally distributed. They were in their 70s. Around 42% were female, so we had a quite high representation of female subjects, and about 50% of patients with ischemic etiology. And I think that that population were fairly typical for those who are now acutely admitted to the hospital.
So let me get back to the results. The primary endpoint, total heart failure hospitalization and cardiovascular death, the rate ratio was 0.79, so 21% reduction, which was statistically nearly significant with P value of 0.059. But the component of primary endpoint, which is total heart failure hospitalization, the rate ratio was 0.74, so 26% reduction, and this was statistically important with 0.013.
Let me just remind you that cardiovascular death was not affected, but because the study was influenced by COVID pandemia, this is why we decided to do the prespecified sensitivity analysis in which we censored in each country all patients at the day when the first case in each country was reported. It was prespecified, and it was, I thoroughly believe, first kind of a reaction and first trial reported in these circumstances. In this sensitivity analysis, all primary and secondary endpoints but cardiovascular death were significantly improved by ferric carboxymaltose. This would be my summary of the AFFIRM-AHF trial.
Dr. Butler:
Congratulations on leading this trial. Now that we know the data, how do these data inform patient care going forward?
Dr. Ponikowski:
Iron deficiency is common in acute heart failure. Iron deficiency can be easily detected using a simple blood test. Number 3, iron deficiency should be assessed in patients hospitalized with acute heart failure with this simple blood test. And now we can say this is an important therapeutic target in this high-risk population. That’s exactly what Gerasimos said – in stable – but only not in the context of improving quality of life, but also in the context of improving the outcomes, reducing the burden of heart failure hospitalization.
So in conclusion, we need to proceed with the message that administration of ferric carboxymaltose, administration of intravenous iron in patients with iron deficiency stabilized after episode of acute heart failure reduces the risk of subsequent heart failure hospitalizations. I think this is the message we need to – or the messages we need to come across and make the awareness that it’s worthy to take into consideration in our clinical practice.
Dr. Butler:
So, Dr. Filippatos, what are your thoughts? And also, what about other types of IV iron?
Dr. Filippatos:
Thank you, Javed. I think that after the results of the AFFIRM Acute Heart Failure trials, but also taking into consideration the totality of evidence, ferric carboxymaltose should be included in the pre-discharge treatment plan of patients with iron deficiency hospitalized for acute heart failure. About the other IV irons, as you know, in small trials, also iron sucrose, sodium ferric gluconate, iron isomaltoside have been used, but the evidence in heart failure is with ferric carboxymaltose for now until today.
Dr. Butler:
What additional trials are ongoing around iron deficiency, Dr. Filippatos? And what will they add to what we already know from AFFIRM-AHF?
Dr. Filippatos:
Yes, there are 3 big ongoing morbidity and mortality trials: the IRONMAN in UK with iron isomaltoside sponsored also by the UK government, the FAIR-HF II in Europe also sponsored by the German government funds, and in US you have, as you know, the HEART-FID also in patients with heart failure and reduced ejection fraction. All these trials, I think they will give us the information that is missing about cardiovascular mortality, but also will give us information in a broad population, broader population around the world. And I think there is another very important trial ongoing, the FAIR-HFpEF, the FAIR in patients with heart failure with preserved ejection fraction that will evaluate functional class improvement and quality of life, and I think this is also an important trial because it will give us for the first time information for patients that we don’t have information on iron deficiency.
I think all these important trials and the totality of evidence from these trials will help us understand better the iron deficiency in the totality of population of patients with heart failure reduced but also preserved ejection fraction.
Dr. Butler:
So that’s great. I’m really looking forward to seeing these results. So in our last few minutes today, I’ll ask each of you to provide your one take-home message for our audience. So, Dr. Filippatos, why don’t you go first this time?
Dr. Filippatos:
I think, Javed, that the take-home message from this American Heart Association Congress from the presentation of AFFIRM Acute Heart Failure trials, but also from the totality of evidence from the previous trials, is the patients hospitalized with acute heart failure should be assessed for iron deficiency, and when iron deficiency is present, should be treated to improve outcomes and decrease heart failure hospitalization.
Dr. Butler:
And, Dr. Ponikowski, your perspective? Your last message for us?
Dr. Ponikowski:
I can only fully concur with what Gerasimos said. So for those who are treating patients with heart failure, acutely admitted, please remember that iron deficiency is one of the most common comorbidities affecting up to 75%, 80% of these patients. As we all say, this is easy to be detected using a simple blood test if only we remember to do this test before hospital discharge. And exactly what Gerasimos said, if you have iron deficiency, detect it, so once patients are ready to go home, please remember that we have ferric carboxymaltose, which can be given intravenously. And please remember that in our study, 1 to 2 injections of ferric carboxymaltose in vast majority of patients resulted in such significant improvement in the outcome, reduction of heart failure rehospitalization. So that would be my take-home message.
Dr. Butler:
I could not agree more. From what we have learned today are 2 facts. One, that screening for iron deficiency in our patients who are hospitalized with acute heart failure is really important because these patients are at really high risk for adverse events post-discharge, and iron deficiency is very common in these patients. But moreover, what we learned from AFFIRM-AHF, that treatment of that iron deficiency can substantially improve the outcomes of these patients and reduce the risk of recurrent hospitalization.
Well, that’s all the time we have today. Thank you to our audiences for listening in and to Drs. Ponikowski and Filippatos for joining me. It was a pleasure speaking with you both.
Dr. Filippatos:
It was a great pleasure and honor to be here discussing the results of AFFIRM Acute Heart Failure with you, Piotr and Javed. Thank you very much for the invitation.
Dr. Ponikowski:
Javed, Gerasimos, thank you very much for this great chat. Thank you for the invitation. Thank you for the opportunity for raising the awareness about iron deficiency and the opportunity to present AFFIRM-AHF data. Thank you.
Announcer:
You have been listening to CME on ReachMD. This activity is provided by Medtelligence and is supported by an independent educational grant from Vifor Pharma.
To receive your free CME credit, or to download this activity, go to ReachMD.com/heartfailure Thank you for listening.
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