Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

AFFIRM-AHF Investigators; Piotr Ponikowski; Bridget-Anne Kirwan; Stefan D. Anker; Theresa McDonagh; Maria Dorobantu; Jaroslaw Drozdz; Vincent Fabien; Gerasimos Filippatos; Udo Michael Gohring; Andre Keren; Irakli Khintibidze; Hans Kragten; Felipe A. Martinez; Marco Metra; Davor Milicic; Jose C. Nicolau; Marcus Ohlsson; Alexander Parkhomenko; Domingo A. Pascual-Figal; Frank Ruschitzka; David Sim; Hadi Skouri; Peter van der Meer; Basil S. Lewis; Josep Comin-Colet; Stephan von Haehling; Alain Cohen-Solal; Nicolas Danchin; Wolfram Doehner; Henry J. Dargie; Michael Motro; Javed Butler; Tim Friede; Klaus H. Jensen; Stuart Pocock; Ewa A. Jankowska

doi:10.1016/S0140-6736(20)32339-4

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

AFFIRM-AHF Investigators, Piotr Ponikowski^*, Bridget-Anne Kirwan, Stefan D. Anker, Theresa McDonagh, Maria Dorobantu, Jaroslaw Drozdz, Vincent Fabien, Gerasimos Filippatos, Udo Michael Gohring, Andre Keren, Irakli Khintibidze, Hans Kragten, Felipe A. Martinez, Marco Metra, Davor Milicic, Jose C. Nicolau, Marcus Ohlsson, Alexander Parkhomenko, Domingo A. Pascual-FigalFrank Ruschitzka, David Sim, Hadi Skouri, Peter van der Meer, Basil S. Lewis, Josep Comin-Colet, Stephan von Haehling, Alain Cohen-Solal, Nicolas Danchin, Wolfram Doehner, Henry J. Dargie, Michael Motro, Javed Butler, Tim Friede, Klaus H. Jensen, Stuart Pocock, Ewa A. Jankowska

^*Corresponding author for this work

Cardiovascular Centre (CVC)

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Abstract

Background Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.

Methods AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Findings Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57.2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72.5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0.79, 95% CI 0.62-1.01, p=0.059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0.80, 95% CI 0.64-1.00, p=0.050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0.96, 95% CI 0.70-1.32, p=0.81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0.74; 95% CI 0.58-0.94, p=0.013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0.80, 95% CI 0.66-0.98, p=0.030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0.67, 95% CI 0.47-0.97, p=0.035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.

Interpretation In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

Original language	English
Pages (from-to)	1895-1904
Number of pages	10
Journal	LANCET
Volume	396
Issue number	10266
DOIs	https://doi.org/10.1016/S0140-6736(20)32339-4
Publication status	Published - 12-Dec-2020

Keywords

HOSPITALIZATIONS
TOLVAPTAN
MORTALITY
DEATH
RISK

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Ferric carboxymaltose for iron deficiency at discharge after acute heart failureFinal publisher's version, 730 KBLicence: Taverne

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AFFIRM-AHF Investigators, Ponikowski, P., Kirwan, B.-A., Anker, S. D., McDonagh, T., Dorobantu, M., Drozdz, J., Fabien, V., Filippatos, G., Gohring, U. M., Keren, A., Khintibidze, I., Kragten, H., Martinez, F. A., Metra, M., Milicic, D., Nicolau, J. C., Ohlsson, M., Parkhomenko, A., ... Jankowska, E. A. (2020). Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. LANCET, 396(10266), 1895-1904. https://doi.org/10.1016/S0140-6736(20)32339-4

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title = "Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial",

abstract = "Background Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.Methods AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritinFindings Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57.2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72.5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0.79, 95% CI 0.62-1.01, p=0.059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0.80, 95% CI 0.64-1.00, p=0.050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0.96, 95% CI 0.70-1.32, p=0.81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0.74; 95% CI 0.58-0.94, p=0.013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0.80, 95% CI 0.66-0.98, p=0.030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0.67, 95% CI 0.47-0.97, p=0.035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.Interpretation In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.",

keywords = "HOSPITALIZATIONS, TOLVAPTAN, MORTALITY, DEATH, RISK",

author = "{AFFIRM-AHF Investigators} and Piotr Ponikowski and Bridget-Anne Kirwan and Anker, {Stefan D.} and Theresa McDonagh and Maria Dorobantu and Jaroslaw Drozdz and Vincent Fabien and Gerasimos Filippatos and Gohring, {Udo Michael} and Andre Keren and Irakli Khintibidze and Hans Kragten and Martinez, {Felipe A.} and Marco Metra and Davor Milicic and Nicolau, {Jose C.} and Marcus Ohlsson and Alexander Parkhomenko and Pascual-Figal, {Domingo A.} and Frank Ruschitzka and David Sim and Hadi Skouri and {van der Meer}, Peter and Lewis, {Basil S.} and Josep Comin-Colet and {von Haehling}, Stephan and Alain Cohen-Solal and Nicolas Danchin and Wolfram Doehner and Dargie, {Henry J.} and Michael Motro and Javed Butler and Tim Friede and Jensen, {Klaus H.} and Stuart Pocock and Jankowska, {Ewa A.}",

year = "2020",

month = dec,

day = "12",

doi = "10.1016/S0140-6736(20)32339-4",

language = "English",

volume = "396",

pages = "1895--1904",

journal = "LANCET",

issn = "0140-6736",

publisher = "ELSEVIER SCIENCE INC",

number = "10266",

}

AFFIRM-AHF Investigators, Ponikowski, P, Kirwan, B-A, Anker, SD, McDonagh, T, Dorobantu, M, Drozdz, J, Fabien, V, Filippatos, G, Gohring, UM, Keren, A, Khintibidze, I, Kragten, H, Martinez, FA, Metra, M, Milicic, D, Nicolau, JC, Ohlsson, M, Parkhomenko, A, Pascual-Figal, DA, Ruschitzka, F, Sim, D, Skouri, H, van der Meer, P, Lewis, BS, Comin-Colet, J, von Haehling, S, Cohen-Solal, A, Danchin, N, Doehner, W, Dargie, HJ, Motro, M, Butler, J, Friede, T, Jensen, KH, Pocock, S & Jankowska, EA 2020, 'Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial', LANCET, vol. 396, no. 10266, pp. 1895-1904. https://doi.org/10.1016/S0140-6736(20)32339-4

TY - JOUR

T1 - Ferric carboxymaltose for iron deficiency at discharge after acute heart failure

T2 - a multicentre, double-blind, randomised, controlled trial

AU - AFFIRM-AHF Investigators

AU - Ponikowski, Piotr

AU - Kirwan, Bridget-Anne

AU - Anker, Stefan D.

AU - McDonagh, Theresa

AU - Dorobantu, Maria

AU - Drozdz, Jaroslaw

AU - Fabien, Vincent

AU - Filippatos, Gerasimos

AU - Gohring, Udo Michael

AU - Keren, Andre

AU - Khintibidze, Irakli

AU - Kragten, Hans

AU - Martinez, Felipe A.

AU - Metra, Marco

AU - Milicic, Davor

AU - Nicolau, Jose C.

AU - Ohlsson, Marcus

AU - Parkhomenko, Alexander

AU - Pascual-Figal, Domingo A.

AU - Ruschitzka, Frank

AU - Sim, David

AU - Skouri, Hadi

AU - van der Meer, Peter

AU - Lewis, Basil S.

AU - Comin-Colet, Josep

AU - von Haehling, Stephan

AU - Cohen-Solal, Alain

AU - Danchin, Nicolas

AU - Doehner, Wolfram

AU - Dargie, Henry J.

AU - Motro, Michael

AU - Butler, Javed

AU - Friede, Tim

AU - Jensen, Klaus H.

AU - Pocock, Stuart

AU - Jankowska, Ewa A.

PY - 2020/12/12

Y1 - 2020/12/12

N2 - Background Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.Methods AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritinFindings Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57.2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72.5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0.79, 95% CI 0.62-1.01, p=0.059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0.80, 95% CI 0.64-1.00, p=0.050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0.96, 95% CI 0.70-1.32, p=0.81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0.74; 95% CI 0.58-0.94, p=0.013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0.80, 95% CI 0.66-0.98, p=0.030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0.67, 95% CI 0.47-0.97, p=0.035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.Interpretation In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

AB - Background Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.Methods AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritinFindings Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57.2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72.5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0.79, 95% CI 0.62-1.01, p=0.059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0.80, 95% CI 0.64-1.00, p=0.050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0.96, 95% CI 0.70-1.32, p=0.81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0.74; 95% CI 0.58-0.94, p=0.013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0.80, 95% CI 0.66-0.98, p=0.030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0.67, 95% CI 0.47-0.97, p=0.035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.Interpretation In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

KW - HOSPITALIZATIONS

KW - TOLVAPTAN

KW - MORTALITY

KW - DEATH

KW - RISK

U2 - 10.1016/S0140-6736(20)32339-4

DO - 10.1016/S0140-6736(20)32339-4

M3 - Article

SN - 0140-6736

VL - 396

SP - 1895

EP - 1904

JO - LANCET

JF - LANCET

IS - 10266

ER -

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial

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