Clinical Cardiovascular Research Lab for the Elderly, Allen Hospital of New York Presbyterian Hospital, 5141 Broadway, 3 Field West, Room 037, New York, NY 10032, USA.
Columbia Mailman School of Public Health, 722 W 168th Street, Rm 630, New York, NY 10032, USA.
J Geriatr Cardiol. 2014 Jun;11(2):100-5. doi: 10.3969/j.issn.1671-5411.2014.02.002.
Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with heart failure with a preserved ejection fraction (HFPEF) and anemia randomized to treatment with epoetin alfa (erythropoiesis-stimulating agents, ESA) vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular (LV) structure, functional capacity, or quality of life (QOL). However, several patients randomized to the treatment arm were non-responders with a suboptimal increase in hemoglobin. All patients in the trial also received oral ferrous gluconate, which could have contributed to increases in hemoglobin observed in those receiving placebo. Accordingly, we performed an analysis separating patients into responders vs. non-responders in order to determine if measured improvement in anemia would have any effect on clinical endpoints.
A total of 56 patients (age 77 ± 11 years, 68% female) were recruited who had anemia defined as a hemoglobin of ≤ 12 g/dL (average, 10.4 ± 1 g/dL) with HFPEF defined as having NHANES-CHF (National Health And Nutrition Examination Survey: Congestive Heart Failure) criteria score of ≥ 3 and an ejection fraction of > 40% (average EF = 63% ± 15%). Patients were randomly allocated to receive either ESA and ferrous gluconate or ferrous gluconate only. In this analysis, a responder was defined as a patient with an increase of 1 g/dL in the first 4 weeks of the trial.
Nineteen subjects were classified as responders compared to 33 non-responders. While the average hemoglobin increased significantly at the end of 6 months for responders (1.8 ± 0.3 vs. 0.8 ± 0.2 g/dL, P = 0.004), 50% of the subjects assigned to ESA were non-responders. Left ventricular function including ejection fraction (P = 0.32) and end diastolic volume (P = 0.59) was unchanged in responders compared to non-responders. Responders also showed no significant improvements in New York Heart Association (NYHA) class, Six Minute Walk Test (6 MWT) and peak VO2. Though QOL improved significantly within each group, there was no difference between the two.
A significant hemoglobin response to anemia treatment with ESA and oral iron does not lead to differences in LV remodeling, functional status, or QOL. Additionally, a significant percent of older adults with HFPEF and anemia do not respond to ESA therapy. Given the results of this small trial, it appears as though using objective improvements in anemia as a marker in older adult subjects with HFPEF does not have significant clinical utility.
最近进行的一项针对社区居住的射血分数保留心力衰竭（HFPEF）合并贫血的老年患者的前瞻性、单盲随机临床试验的先前数据显示，接受促红细胞生成素α（红细胞生成刺激剂，ESA）治疗与安慰剂治疗的患者左心室（LV）结构、功能能力或生活质量（QOL）无显著获益。然而，一些被随机分配到治疗组的患者对治疗没有反应，血红蛋白增加不理想。试验中的所有患者均接受口服葡萄糖酸亚铁治疗，这可能导致接受安慰剂治疗的患者血红蛋白升高。因此，我们进行了一项分析，将患者分为有反应者和无反应者，以确定贫血的改善是否会对临床终点产生任何影响。
共招募了 56 名患者（年龄 77 ± 11 岁，68%为女性），贫血定义为血红蛋白≤12g/dL（平均 10.4 ± 1g/dL），HFPEF 定义为 NHANES-CHF（国家健康和营养检查调查：充血性心力衰竭）标准评分≥3 且射血分数>40%（平均 EF=63%±15%）。患者随机分配接受 ESA 和葡萄糖酸亚铁或仅葡萄糖酸亚铁治疗。在这项分析中，有反应者定义为在试验的前 4 周内血红蛋白增加 1g/dL 的患者。
19 名患者被归类为有反应者，33 名患者为无反应者。虽然在 6 个月时，有反应者的血红蛋白平均显著升高（1.8±0.3 vs. 0.8±0.2g/dL，P=0.004），但 50%接受 ESA 治疗的患者无反应。与无反应者相比，左心室功能（包括射血分数（P=0.32）和舒张末期容积（P=0.59））在有反应者中没有变化。有反应者在纽约心脏协会（NYHA）分级、6 分钟步行试验（6MWT）和峰值 VO2 方面也没有显著改善。尽管两组的生活质量均显著改善，但两组之间无差异。
ESA 和口服铁治疗贫血的血红蛋白显著反应并不能导致 LV 重塑、功能状态或 QOL 的差异。此外，HFPEF 和贫血的老年患者中，有相当大比例的患者对 ESA 治疗无反应。鉴于这项小型试验的结果，使用 HFPEF 老年患者贫血的客观改善作为标志物似乎没有显著的临床意义。
