Piotr Ponikowski1, Bridget-Anne Kirwan2, Stefan D Anker3, Theresa McDonagh4, Maria Dorobantu5, Jarosław Drozdz6, Vincent Fabien7, Gerasimos Filippatos8, Udo Michael Göhring7, Andre Keren9, Irakli Khintibidze10, Hans Kragten11, Felipe A Martinez12, Marco Metra13, Davor Milicic14, José C Nicolau15, Marcus Ohlsson16, Alexander Parkhomenko17, Domingo A Pascual-Figal18, Frank Ruschitzka19, David Sim20, Hadi Skouri21, Peter van der Meer22, Basil S Lewis23, Josep Comin-Colet24, Stephan von Haehling25, Alain Cohen-Solal26, Nicolas Danchin27, Wolfram Doehner3, Henry J Dargie28, Michael Motro29, Javed Butler30, Tim Friede31, Klaus H Jensen7, Stuart Pocock32, Ewa A Jankowska33. 1. Department of Heart Diseases, Wrocław Medical University, Wroclaw, Poland; Center for Heart Diseases, University Hospital in Wrocław, Wroclaw, Poland. Electronic address: piotr.ponikowski@umed.wroc.pl. 2. Department of Clinical Research, SOCAR Research, Nyon, Switzerland; London School of Hygiene & Tropical Medicine, University College London, London, UK. 3. Charité, Campus Virchow-Klinikum, Berlin, Germany. 4. King's College Hospital, London, UK; School of Cardiovascular Medicine & Sciences, King's College London, London, UK. 5. Cardiology Department, Emergency Hospital of Bucharest, Bucharest, Romania. 6. Klinika Kardiologii, Uniwersytet Medyczny w Łodzi, Lodz, Poland. 7. Vifor Pharma, Glattbrugg, Switzerland. 8. Department of Cardiology, Heart Failure Unit, National and Kapodistrian University of Athens, Athens, Greece. 9. Hadassah Medical Center, Department of Cardiology, Jerusalem, Israel. 10. Aleksandre Aladashvili Clinic, Tbilisi, Georgia. 11. Maastricht University Medical Center, Heerlen, Netherlands. 12. Universidad Nacional de Córdoba, International Society of Cardiovascular Pharmacotherapy, Córdoba, Argentina. 13. Department of Cardiology, University and Civil Hospital, Brescia, Italy. 14. University Hospital Center Zagreb, Zagreb, Croatia. 15. Instituto do Coracao (InCor), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. 16. Department of Internal Medicine, Malmö University Hospital, Malmö, Sweden. 17. M D Strazhesko Institute of Cardiology, Kyiv, Ukraine. 18. Cardiology Department, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain. 19. UniversitätsSpietal Zürich, Klinik für Kardiologie, Zürich, Switzerland. 20. National Heart Center, Clinical Translational and Research Office, Singapore. 21. American University of Beirut, Medical Center Beirut, Beirut, Lebanon. 22. University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands. 23. Lady Davis Carmel Medical Center, Clinical Cardiovascular Research Institute, Haifa, Israel. 24. Hospital Universitari Bellvitge, Barcelona, Spain. 25. University Medical Center Göttingen, Göttingen, Germany. 26. Hospital Lariboisière, INSERM, Paris, France. 27. European Hospital Georges Pompidou, Paris, France. 28. Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK. 29. Sheba Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel. 30. University of Mississippi Medical Center, Jackson, MS, USA. 31. University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Göttingen partner site, Göttingen, Germany. 32. Department of Clinical Research, SOCAR Research, Nyon, Switzerland. 33. Department of Heart Diseases, Wrocław Medical University, Wroclaw, Poland; Center for Heart Diseases, University Hospital in Wrocław, Wroclaw, Poland.
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 <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. 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 withferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.
RCT Entities:
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 <100 μg/L, or 100-299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. 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. FUNDING: Vifor Pharma.
Authors: Norbert Gattermann; Martina U Muckenthaler; Andreas E Kulozik; Georgia Metzgeroth; Jan Hastka Journal: Dtsch Arztebl Int Date: 2021-12-10 Impact factor: 5.594
Authors: Fabiana G Marcondes-Braga; Lídia Ana Zytynski Moura; Victor Sarli Issa; Jefferson Luis Vieira; Luis Eduardo Rohde; Marcus Vinícius Simões; Miguel Morita Fernandes-Silva; Salvador Rassi; Silvia Marinho Martins Alves; Denilson Campos de Albuquerque; Dirceu Rodrigues de Almeida; Edimar Alcides Bocchi; Felix José Alvarez Ramires; Fernando Bacal; João Manoel Rossi Neto; Luiz Claudio Danzmann; Marcelo Westerlund Montera; Mucio Tavares de Oliveira Junior; Nadine Clausell; Odilson Marcos Silvestre; Reinaldo Bulgarelli Bestetti; Sabrina Bernadez-Pereira; Aguinaldo F Freitas; Andréia Biolo; Antonio Carlos Pereira Barretto; Antônio José Lagoeiro Jorge; Bruno Biselli; Carlos Eduardo Lucena Montenegro; Edval Gomes Dos Santos Júnior; Estêvão Lanna Figueiredo; Fábio Fernandes; Fabio Serra Silveira; Fernando Antibas Atik; Flávio de Souza Brito; Germano Emílio Conceição Souza; Gustavo Calado de Aguiar Ribeiro; Humberto Villacorta; João David de Souza Neto; Livia Adams Goldraich; Luís Beck-da-Silva; Manoel Fernandes Canesin; Marcelo Imbroinise Bittencourt; Marcely Gimenes Bonatto; Maria da Consolação Vieira Moreira; Mônica Samuel Avila; Otavio Rizzi Coelho Filho; Pedro Vellosa Schwartzmann; Ricardo Mourilhe-Rocha; Sandrigo Mangini; Silvia Moreira Ayub Ferreira; José Albuquerque de Figueiredo Neto; Evandro Tinoco Mesquita Journal: Arq Bras Cardiol Date: 2021-06 Impact factor: 2.000
Authors: Amr Abdin; Johann Bauersachs; Norbert Frey; Ingrid Kindermann; Andreas Link; Nikolaus Marx; Mitja Lainscak; Jonathan Slawik; Christian Werner; Jan Wintrich; Michael Böhm Journal: Clin Res Cardiol Date: 2021-05-13 Impact factor: 5.460
Authors: Murilo Guedes; Daniel G Muenz; Jarcy Zee; Brian Bieber; Benedicte Stengel; Ziad A Massy; Nicolas Mansencal; Michelle M Y Wong; David M Charytan; Helmut Reichel; Sandra Waechter; Ronald L Pisoni; Bruce M Robinson; Roberto Pecoits-Filho Journal: J Am Soc Nephrol Date: 2021-07-08 Impact factor: 14.978