波兰瓦罗克医科大学Piotr Ponikowski团队研究了羧基麦芽糖铁治疗急性心力衰竭后出院时缺铁患者的疗效。2020年11月13日，该研究发表在《柳叶刀》杂志上。

静脉内注射羧基麦芽糖铁可改善慢性心力衰竭和铁缺乏症患者的症状和生活质量。为了评估与安慰剂相比，羧基麦芽糖铁对急性心力衰竭发作后稳定期患者预后的影响，研究组在欧洲、南美和新加坡的121个研究点进行了一项多中心、双盲、随机试验。

2017年3月21日至2019年7月30日，研究组招募了1108例年龄在18岁及以上，因急性心力衰竭伴铁缺乏症住院，且左室射血分数小于50％的患者。出院前根据铁缺乏程度将患者按1：1随机分组，其中558例接受长达24周的静脉内羧基麦芽糖铁治疗，550例接受安慰剂治疗。主要结局为52周时因心力衰竭和心血管死亡而住院的总人数。

羧基麦芽糖铁组共有293例患者发生主要结局（每100患者-年57.2例），安慰剂组共有372例（每100患者-年72.5例），比率（RR）为0.79。羧基麦芽糖铁组共发生370例心血管疾病住院和心血管死亡，安慰剂组为451例，RR为0.80。两组间的心血管死亡率没有差异，均为14%。

羧基麦芽糖铁组共有217例患者因心力衰竭而住院，安慰剂组有294例，RR为0.74。羧基麦芽糖铁组有181名患者（32％）发生了首次心力衰竭住院或心血管死亡的综合事件，安慰剂组有209名（38％），差异显著。与安慰剂相比，羧基麦芽糖铁组患者因心力衰竭住院和心血管死亡损失的天数更少。羧基麦芽糖铁组中有45％的患者发生严重不良事件，安慰剂组有51％。

研究结果表明，对于缺铁、左心室射血分数低于50%且急性心力衰竭发作后病情稳定的患者，用羧基麦芽糖铁治疗是安全的，可降低心力衰竭住院的风险，并对心血管死亡风险没有明显影响。

附：英文原文

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

Author: Piotr Ponikowski, Bridget-Anne Kirwan, Stefan D Anker, Theresa McDonagh, Maria Dorobantu, Jarosaw Drozdz, Vincent Fabien, Gerasimos Filippatos, Udo Michael Ghring, Andre Keren, Irakli Khintibidze, Hans Kragten, Felipe A Martinez, Marco Metra, Davor Milicic, José 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, G Azize, A Fernandez, GO Zapata, P Garcia Pacho, A Glenny, F Ferre Pacora, ML Parody, J Bono, C Beltrano, A Hershson, N Vita, HA Luquez, HG Cestari, H Fernandez, A Prado, M Berli, R García Durán, J Thierer, M Diez, L Lobo Marquez, RR Borelli, Má Hominal, M Metra, P Ameri, P Agostoni, A Salvioni, L Fattore, E Gronda, S Ghio, F Turrini, M Uguccioni, M Di Biase, M Piepoli, S Savonitto, A Mortara, P Terrosu, A Fucili, G Boriani, P Midi, E Passamonti, F Cosmi, P van der Meer, P Van Bergen, M van de Wetering, NYY Al-Windy, W Tanis, M Meijs, RGEJ Groutars, HKS The, B Kietselaer, HAM van Kesteren, DPW Beelen, J Heymeriks, R Van de Wal, J Schaap, M Emans, P Westendorp, PR Nierop, R Nijmeijer, OC Manintveld, M Dorobantu, DA Darabantiu, D Zdrenghea, DM Toader, L Petrescu, C Militaru, D Crisu, MC Tomescu, G Stanciulescu, A Rodica Dan, LC Iosipescu, DL Serban

Issue&Volume: 2020-11-13

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 with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.

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

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32339-4/fulltext