1- regarding the limitation of this study (look atdiscussion)
a- what limitation describe by the author? are theyaccurate?
b- what limitation have you identified? were they included bythe authors?
c- are any of your identified limitation consider fatal flow ofthe trial? (rending all results inapplicable)
look at Ferric carboxymaltose for iron deficiency at dischargeafter acute heart failure: a multicentre, double-blind, randomised,controlled trials PubMed
this is the discussion can you please read it and from it youcan answer the question:
The findings of AFFIRM-AHF show that, compared with placebo,treatment with ferric carboxymaltose, initiated at hospitaldischarge in stabilised patients with acute heart failure andconcomitant iron deficiency, resulted in an RR for the combinedendpoint of total heart failure hospitalisations and cardiovasculardeath of 0·79 (95% CI 0·62–1·01, p=0·059) which falls just short ofconventional 5% statistical significance. The total
number of heart failure hospitalisations was signifi- cantlylower in the ferric carboxymaltose group com- pared with theplacebo group. Statistically significant treatment benefits offerric carboxymaltose compared with placebo were seen for the timeto first heart failure hospitalisation or cardiovascular death, andfor days lost due to heart failure hospitalisation andcardiovascular death. Patients assigned to ferric carboxymaltosereceived an average total dose of 1352 mg ferric carboxymaltose, upto the maximum treatment period of 24 weeks.
Iron is an essential micronutrient involved in cellular energyand metabolism of both haematopoietic and extrahaematopoietictissues and is thus critical for maintaining body homoeostasis.Iron deficiency in acute heart failure is characterised by depletedbody iron stores accompanied by unmet cellular iron requirementsfor maintenance of energetic homoeostasis at the periphery, thusimpacting negatively on the haematopoietic and non-haematopoieticpathways.10,24,25 We showed that in this high-risk population ofpatients with stabilised acute heart failure and concomitant irondeficiency, the total number of heart failure hospitalisations wasreduced with ferric carboxymaltose treatment compared with placebo,irrespective of anaemia status (ie, anaemic or non-anaemic),providing further evidence that ferric carboxymaltose benefitspatients beyond the correction of anaemia.
Our findings suggest a consistent treatment effect acrossseveral predefined subgroups for the primary outcome of total heartfailure hospitalisations and cardiovascular death. We note thatcause of heart failure could be an effect modifier. This might be atopic for future research, given that non-ischaemic heart failureaetiology comprises a heterogeneous group of patients, in whom thepathophysiological consequences of iron deficiency are not yet wellunderstood.
The AFFIRM-AHF cohort had higher annualised event rates for thecombined endpoint of first heart failure hospitalisation orcardiovascular death than in somerecentlypublishedtrials(47·1per100patient-yearsinthe placebo groupcompared with 40·2 per 100 patient-years in the EVEREST placebogroup26 and 37·3 per 100 patient- years in the ASTRONAUT placebogroup27). In addition, patients included in this trial (both groupscombined) presented with highly elevated plasma NT-proBNP (median4684 pg/mL compared with 2718 pg/mL in ASTRONAUT27). These datasuggest that for patients admitted with acute heart failure, theidentification and treatment of comorbidities such as irondeficiency should be a routine component of the treatmentstrategy.
This is one of the first randomised clinical trials reportingresults in which data collection, follow-up, and the analyses werepotentially affected by the COVID-19 pandemic. The prespecifiedpre-COVID-19 sensitivity analysis showed a significant benefit offerric carboxymaltose on the combined endpoint of total heartfailure hospitalisations and cardiovascular death. At the
initial outbreak of the COVID-19 pandemic in February to March,2020, patient follow-up was continuing but all patients hadcompleted their week 24 visit (ie, the last visit for theadministration of study treatment in patients in whom irondeficiency persisted). Both patient safety and the potential impactof COVID-19 on the data integrity and completeness of follow-up wasdiscussed in detail between the trial sponsor and steeringcommittee, and several mitigation plans were implemented. Forexample, patients could be contacted by telephone for the plannedstudy visits instead of returning to the outpatient clinic visitplanned by the study protocol. The number of heart failure hospi-talisations was reportedly reduced by 40% in Europe between Marchand June, 2020.19 We are unable to predict what influence COVID-19might have had on a treatment effect, but it is plausible that lesscomplete follow-up, fewer hospitalisations, and a general lack ofprotocol compliance could have diluted the ability to observetreatment differences. Thus, we consider our prespecified COVID-19sensitivity a judicious analysis.
In patients with iron deficiency, a left ventricular ejectionfraction of less than 50%, and who had stabilised after an episodeof acute heart failure, treatment with ferric carboxymaltose wassafe and reduced the risk of heart failure hospitalisations but hadno apparent effect on the risk of cardiovascular death.
