Late-breaking First Response on AFFIRM-AHF

Announcer:
This activity, entitled, “Late-Breaking First Response on Affirm AH” is provided by Medtelligence, and is supported by an independent educational grant from Vifor Pharma.

Dr. Anker:
Hello, everybody. My name is Stefan Anker from Berlin, Germany and here we are after the late breakout presentation for the AFFIRM-AHF trial, and in the first response, video-commenting here with me are today Ewa Jankowska, Javed Butler and Josep Comin-Colet. Really I’m looking forward to the comments.

Dr. Jankowska:
The AFFIRM-AHF trial was designed to evaluate the effect of intravenous ferric carboxymaltose, compared to placebo, initiated shortly before hospital discharge in patients with acute heart failure and iron deficiency on recurrent heart failure hospitalization and cardiovascular death during the follow-up to 52 weeks after randomization. There were 1,108 patients participating in this trial across Europe, South America, Lebanon, Israel and Singapore, and the principal findings of this trial demonstrated that treatment with ferric carboxymaltose, as compared to placebo, resulted in a rate ratio with a combined endpoint of total heart failure hospitalizations and cardiovascular death of 0.79, with a P-value of 0.059. It’s really important to emphasize that this result was driven by the total number of heart failure hospitalizations, because the total number of heart failure hospitalizations was significantly lower, by around 26%, in the ferric carboxymaltose group as compared with the placebo group. Our trial is one of the first trials reporting the results in which data collection and follow-up could be potentially affected by the COVID-19 pandemia. It’s important to acknowledge that the statistical analysis plan was established before locking the database, and this plan included a specific pre-COVID-19 sensitivity analysis, which was based on that, that patients’ follow-up was censored in each country, at the date when its first COVID-19 patients was reported. Importantly, this pre-specified pre-COVID sensitivity analysis showed a statistically significant benefit of ferric carboxymaltose on the combined endpoint of total heart failure hospitalizations and cardiovascular death. Obviously, we are not able to predict exactly what influence COVID-19 might have had on the treatment effect. However, it is quite possible that less complete follow-up to a hospitalization could have diluted the treatment effect. Therefore we consider this pre-COVID sensitivity analysis as important, in the context of interpretation of the results of our trial. Our data suggests that for patients admitted with acute heart failure, the identification and treatment of comorbidities, such as iron deficiency, should be a routine component of the diagnostic and treatment strategy. The results of the AFFIRM-AHF trial support the recommendation to administer this therapy with ferric carboxymaltose for iron-deficient patients after an episode of acute heart failure, in order to prevent recurrent heart failure hospitalizations.

Dr. Anker:
Now, everybody, what is your first response to the AFFIRM-AHF data?  What do you really think is this data adding to what we already know about ferric carboxymaltose, about IV iron, for patients with heart failure? 

Dr. Comin-Colet:
This this view that is gonna give us new tools to treat patients in a very particular phase of their disease – the phase, we call it the bull level phase. So it means that now we’re going to have a treatment that can be applied in patients before this chart. And this treatment, and this case replenishing patients with intravenous iron we make attention the risk of readmission in this particular period. And along with this reduction of the risk of readmission, we’re probably gonna see an improvement their quality of life.

Dr. Anker:
So Javed, tell me, how do you as clinicians view this?  How do you think will this impact on the way U.S. clinicians practice for heart failure patients in the context of iron deficiency? 

Dr. Butler:
So the impact of AFFIRM-AHF trial on clinical practice in U.S. is yet to be seen. We’ll see how the regulatory agencies look at this data, and then how the Guidelines Committee look at these data. But at least looking at these data, my initial reaction, or opinion, is that this will definitely have an impact on the management of patients with heart failure reduced ejection fraction. We have been really lucky in heart failure with reduced ejection fraction, with a lot of positive clinical trials with pharmacotherapy, but they are kinda, sorta diffused for all patients, and there’s a lot of debate which patient should get which therapy, in what sequence. Here, we have a very specific disease entity, which is iron deficiency, regardless whether you have anemia or not, and that – in this is specific population, we have a specific target which is to treat iron deficiency with IV iron. And, now we have the data that not only does it improve really important patient-reported outcomes, like functional capacity and quality of life and symptomatology, but actually improve clinical endpoints as well – reduce the risk of recurrent hospitalizations in patients with heart failure reduced ejection fraction – that I think in my opinion, that clinicians will be more cognizant of checking for iron deficiency in patients with heart failure and replacing it when iron deficiency is detected, and I think our patients will be benefiting from this yet another therapy. But I think the biggest thing is that this is a targeted therapy, and that actually helps the clinical implementation.

Dr. Anker:
No, thanks a lot. These are all great thoughts. I think that really we have seen here a very innovative trial design, in an important area, which is discharged from hospital. We know that ferric carboxymaltose can help with this, with a really clinically meaningful difference in re-hospitalization events. We know this therapy works from other trials for quality of life and symptoms, and now we also know we can prevent re-hospitalizations. Very good results, indeed. 

Announcer:
This activity is provided by Medtelligence, and is supported by an independent educational grant from Vifor Pharma. Thank you for listening.