Ezekowitz Justin A, Mulder Hillary, Mentz Robert J, Butler Javed, DE Pasquale Carmine G, Lewis Gregory D, O'Meara Eileen, Ponikowski Piotr, Troughton Richard W, Wong Yee Weng, Adamczyk Robert, Numan Syed, Blackman Nicole, Rockhold Frank W, Hernandez Adrian F
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
J Card Fail. 2025 Jan 29. doi: 10.1016/j.cardfail.2025.01.009.
The HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose [FCM] as Treatment for Heart Failure with Iron Deficiency) is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) vs placebo in patients with heart failure and iron deficiency. The results showed a modest but nonstatistically significant reduction in important clinical outcomes, including all-cause mortality.
We sought to understand the factors associated with all-cause mortality.
Data concerning patients enrolled in the HEART-FID trial were used to determine factors associated with all-cause mortality via multivariable models. The models included key clinical characteristics, including treatment interactions identified in the primary analysis (age by sex and country of enrollment). All-cause mortality at 12 months and over the full duration of follow-up (median 23.1 months) was evaluated by using Cox proportional hazard regression.
A total of 3065 patients had 737 all-cause mortality events over the duration of the trial, with 289 events occurring in the first 12 months. Fewer patients randomized to FCM died by 12 months compared with the placebo group (131 receiving FCM vs 158 receiving placebo; hazard ratio 0.82 [95% confidence interval: 0.65-1.04]). Patients who died were more likely to be older and to have diabetes, atrial fibrillation, lower ejection fractions and estimated glomerular filtration rates and higher N-Terminal pro B-type natriuretic peptide (NT-proBNP) levels. The 3 multivariable factors most strongly associated with all-cause mortality at 12 months were NT-proBNP level, country of enrollment and 6-minute walk test distance. Similar results were seen for predicting all-cause mortality over the entire follow-up; the addition of an age × sex × FCM interaction yielded statistically significant results, with greater association of benefit from FCM found in older women than in other subgroups of patients.
FCM, compared with placebo, was associated with a potentially clinically meaningful (but not statistically significant) reduction in all-cause mortality, with key predictors of mortality being natriuretic peptide level, country of enrollment and 6-minute walk test distance.
HEART-FID试验（羧基麦芽糖铁[FCM]治疗缺铁性心力衰竭的随机安慰剂对照试验）是测试静脉注射铁剂（羧基麦芽糖铁[FCM]）与安慰剂治疗心力衰竭合并缺铁患者的最大规模试验。结果显示，包括全因死亡率在内的重要临床结局有适度但无统计学意义的降低。
我们试图了解与全因死亡率相关的因素。
利用HEART-FID试验中登记患者的数据，通过多变量模型确定与全因死亡率相关的因素。这些模型包括关键临床特征，包括在初步分析中确定的治疗相互作用（年龄、性别和登记国家）。使用Cox比例风险回归评估12个月及整个随访期（中位时间23.1个月）的全因死亡率。
在试验期间，共有3065例患者发生737例全因死亡事件，其中289例发生在最初12个月内。与安慰剂组相比，随机接受FCM治疗的患者在12个月时死亡人数较少（131例接受FCM治疗，158例接受安慰剂治疗；风险比0.82[95%置信区间：0.65-1.04]）。死亡患者更可能年龄较大，患有糖尿病、心房颤动，射血分数和估计肾小球滤过率较低，N末端B型利钠肽原（NT-proBNP）水平较高。12个月时与全因死亡率最密切相关的3个多变量因素是NT-proBNP水平、登记国家和6分钟步行试验距离。在预测整个随访期的全因死亡率方面也得到了类似结果；加入年龄×性别×FCM相互作用产生了具有统计学意义的结果，发现老年女性从FCM中获益的关联性大于其他患者亚组。
与安慰剂相比，FCM与全因死亡率有潜在的临床意义降低（但无统计学意义），死亡率的关键预测因素是利钠肽水平、登记国家和6分钟步行试验距离。
