Intravenous Iron Reduces HF Readmissions: AFFIRM-AHF

Iron supplementation reduces coronary heart failure (HF) readmissions in iron-deficient patients hospitalized for acute HF, per outcomes of the AFFIRM-AHF trial. 

After 52 weeks, intravenous ferric carboxymaltose (Ferinject) reduced the threat of total HF hospitalizations and cardiovascular (CV) loss of life by 21% when compared with placebo (293 vs 372 occasions; price ratio [RR] 0.79; 95% CI, 0.62 – 1.01).

Though the composite essential endpoint failed to enact statistical significance, it became pushed by a serious 26% reduction within the threat of total HF properly being center readmissions (P = .013) without an terminate on CV mortality (P =.809).

Since the administration and apply-up of patients became plagued by the COVID-19 pandemic, a prespecified sensitivity diagnosis became performed that censored patients in each and every nation on the date when its first COVID-19 affected person became reported, explained predominant investigator Piotr Ponikowski, MD, PhD, Wroclaw Scientific University, Wroclaw, Poland. 

That diagnosis revealed a serious 30% reduction in total HF readmissions (P = .005) in patients receiving ferric carboxymaltose (FCM), as properly as significant advantages on the essential composite and secondary endpoints.

Particularly, 80% of patients required perfect one or two injections and HF hospitalizations own been reduced no subject anemia home.

“Iron deficiency wants to be searched in patients hospitalized with acute coronary heart failure — assessed the usage of a straightforward blood take a look at — and is now the most important therapeutic target,” Ponikowski acknowledged on the digital American Coronary heart Association (AHA) Scientific Lessons 2020. 

The outcomes own been additionally revealed concurrently in The Lancet.

Iron deficiency is most up-to-date in as much as 70% of patients with acute HF and a predictor of awful consequence, fair of anemia and ejection portion, he famed.

The FAIR-HF, CONFIRM-HF, and EFFECT-HF trials demonstrated that IV iron supplementation improves command ability, indicators, and quality of life in iron-deficient HF patients.

On the opposite hand, no such profit became considered with oral IV within the IRONOUT trial. “So it looks if we’re to exchange iron, it wants to be carried out the usage of intravenous therapy,” acknowledged John McMurray, MD, University of Glasgow, Scotland, who became invited to chat concerning the outcomes.

He seen that the reduction in HF hospitalizations in AFFIRM-AHF own been reasonably modest and that the trial became never anticipated to indicate a profit on CV mortality. Additionally, the COVID-19 sensitivity diagnosis offering more convincing effects is a sound attain and one urged by regulators.

Extra, the findings are supported by fair proof in chronic kidney disease, from the PIVOTAL trial, that intravenous iron reduces HF hospitalizations, McMurray acknowledged.

“The million-greenback inquire of, unnecessary to train, is what’s going to the outcomes of this survey indicate for the pointers: I safe they presumably will change the pointers,” he acknowledged. “Undoubtedly, I am hoping they are going to change the US pointers, which own with out a doubt given a with out a doubt lukewarm suggestion for intravenous iron and I safe that must presumably be stronger.”

In a category IIb suggestion, the 2017 American College of Cardiology/AHA/Coronary heart Failure Society of The United States coronary heart failure pointers bellow intravenous iron “will more than likely be reasonable” to again functional home and quality of life in Fresh York Coronary heart Association class II and III patients with iron deficiency.

The 2016 European Society of Cardiology pointers encompass a category IIa suggestion that IV iron “wants to be thought about” in iron-deficient patients with symptomatic HF with reduced ejection portion.

“That is the first colossal-scale [trial] of IV supplementation that will also doubtlessly change the model we attain patients, in particular those with hospitalized coronary heart failure,” previous AHA president Clyde Yancy, MD, MSc, Northwestern University Feinberg College of Medication in Chicago, acknowledged someday of an earlier press briefing.

He identified that clinicians own been circumspect concerning the early IV iron records. “I with out a doubt must congratulate you because you’ve got changed the account,” Yancy acknowledged. “We must start allowing for iron deficiency; now we must safe how we incorporate this in therapy protocols.”

Press briefing panelist Marc Pfeffer, MD, PhD, Brigham and Girls’s Scientific institution and Harvard Scientific College in Boston, acknowledged he became amongst those circumspect.

“I am now not a skeptic and I own to congratulate them for displaying it’s a long way a threat factor,” he acknowledged. “Or not it’s one factor to own a threat factor; it’s another to be a modifiable threat factor and I safe that’s what’s so moving about this.”

The double-blind, section 4 AFFIRM-AHF trial randomly assigned 1132 patients to receive a bolus injection of ferric carboxymaltose or typical saline earlier than properly being center discharge for an acute HF episode. Subsequent therapy became given, as wanted, as much as 24 weeks post-randomization.

At admission, all patients had left ventricular ejection fractions less than 50% and iron deficiency (serum ferritin <100 ng/mL or serum ferritin 100-299 ng/mL if transferrin saturation <20%).

The modified design-to-take care of (mITT) diagnosis integrated 558 FCM patients and 550 controls in whom survey therapy became started and for whom at least one post-randomization mark became accessible.

Table. Important and Secondary Outcomes With FCM

RR, price ratio; HR, hazard ratio

Press briefing discussant Nancy Sweitzer, MD, PhD, director of the University of Arizona’s Sarver Coronary heart Heart in Tucson, acknowledged AFFIRM-AHF is an “significant trial likely to change pointers” and “centered one in all the perfect threat populations now we own in coronary heart failure.”

Patients with iron deficiency are inclined to be elderly with more comorbidities, own longer properly being center lengths of close, and better readmission charges. “So impacting hospitalizations on this inhabitants is amazingly impactful,” she acknowledged.

“Consciousness and overview of iron deficiency are the most important section of inpatient care of patients with ejection fractions less than or equal to 50% and acute decompensated coronary heart failure, and I safe all of us within the neighborhood must pay a long way more consideration to this bellow.”

As with all unique therapy, there are implementation challenges resembling easy the manner to note patients and produce the therapy in a mark-efficient manner, Sweitzer acknowledged.

The trial centered on the most inclined interval for HF patients, but these patients wants to be rechecked every 3 to 4 months for iron deficiency, Ponikowski seen someday of the briefing.

“That is a modifiable threat factor,” he acknowledged. “We perfect must remember, we perfect must assess it, and now we own a with out a doubt, somewhat straightforward design in our hands. We factual must measure two biomarkers, transferrin saturation and ferritin — that is all.”

Unanswered questions encompass the mechanism on the motivate of the reduction in hospitalization, the relationship of profit to hemoglobin phases, and whether there’s a differential profit per age, presence of ischemia, or intercourse, especially as women folk are inclined to be more severely plagued by iron deficiency, Sweitzer acknowledged.

Sooner or later of the formal presentation, Ponikowski acknowledged the essential endpoint became consistent in subgroup analyses all over baseline hemoglobin, estimated glomerular filtration price, and N-terminal genuine-mind natriuretic peptide phases, HF etiology, ejection portion, and whether HF became identified earlier than the index hospitalization.

Medication with FCM became safe, without a significant differences between the FCM and placebo teams in essential unfavorable occasions (45% vs 51%) or unfavorable occasions main to survey discontinuation (18% vs 17%), he reported. Doubtlessly the most well liked unfavorable occasions own been cardiac disorders (40.1% vs 44.3%) and infections (18.2% vs 22%).

AFFIRM-AHF is the first of three ongoing mortality and morbidity trials in coronary heart failure with intravenous ferric carboxymaltose; the others are FAIR-HF2 and HEART-FID. Extra insights are additionally anticipated subsequent yr on intravenous iron isomaltoside from the Scottish-based IRONMAN trial in 1300 HF patients with iron deficiency. 

The survey became sponsored by Vifor World. Ponikowski has purchased be taught grants and non-public costs from Vifor Pharma; and non-public costs from Amgen, Bayer, Novartis, Abbott Vascular, Boehringer Ingelheim, Merck, Pfizer, Servier, AstraZeneca, Berlin Chemie, Cibiem, Renal Guard Choices Bristol-Myers Squibb, and Impulse Dynamics.

Pfeffer reported honoraria from AstraZeneca, Corvidia, GlaxoSmithKline, Jazz, MyoKardia, Novartis, Roche, Sanofi, and Servier; other relationships with DalCor and Novo Nordisk; be taught grants from Novartis; and an possession interest in DalCor. Sweitzer reported be taught payments from Merck and Novartis; and consulting costs from Myocardia.

McMurray reported relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Novartis, and Servier. Yancy reported a relationship with Abbott and JAMA Network.

Lancet. Printed online November 13, 2020. Fleshy textual train

American Coronary heart Association Scientific Lessons 2020: Offered November 13, 2020.  

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