Killing two birds with one stone - The potential of iron supplementation in Chinese HFrEF patients

Sep 29, 2026

Letter to the editor arguing that iron deficiency (ID) may be highly prevalent in Chinese patients with heart failure and reduced ejection fraction (HFrEF), even when anemia status is not present. It highlights low rates of baseline complete ID assessment and discusses links between ACE inhibitors and new anemia and cough. The letter proposes routine iron supplementation for Chinese HFrEF patients receiving ACE inhibitors to address ID and potentially mitigate ACE inhibitor–induced cough, supported by referenced clinical evidence.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages1

Reading Time3 min

AccessFree to download

Letter to the editor

Prevalence of iron deficiency in HFrEF

Assessment of iron status at baseline

ACE inhibitors, anemia, and cough

Rationale for routine iron supplementation

References

J Chin MedAssoc Letter to the editor Killing two birds with one stone: The potential of iron supplementation in Chinese HFrEF patients Chia Siang Kowa,*, Dinesh Sangarran Ramachandramb, Syed Shahzad Hasanc,d aSchool of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; bSchool of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; cSchool of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom; dSchool of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia DEAR EDITOR, We read with interest the study by Sung et al,1 which aimed to assess the prevalence and significance of iron deficiency (ID) in Taiwanese patients with heart failure and reduced ejection fraction (HFrEF) . Among the 3612 included HFrEF patients, 43.6% were found to have ID, irrespective of their anemia status. In fact, we believe that ID might be even more prevalent in this cohort of HFrEF patients than reported in the study. This assumption is based on previous research demonstrating that ferritin levels might not always accurately indicate low iron stores in this population. For instance, in a 2006 series of 37 patients with advanced HF and anemia, most of them (73%) showed no stainable bone marrow iron (indicating ID), despite only two of the iron-deficient patients having reduced serum ferritin levels.2 While the findings underscore the critical importance of carefully monitoring iron status in HFrEF patients, it is noteworthy that only 18.4% of the HFrEF patients in this study underwent complete ID assessment at baseline. However, we are encouraged by the observation that the rate of iron profile testing was significantly higher among patients using renin-angiotensin system (RAS) inhibitors. Specifically, angiotensin-converting enzyme (ACE) inhibitors, known for their beneficial effects on patient survival in heart failure, have been associated with incidence of anemia. In the landmark enalapril trial (Studies of Left Ventricular Dysfunction [SOLVD] study3) which involved patients with left ventricular dysfunction randomly assigned to either enalapril or placebo, it was reported that at 1 year after randomization, the rate of new anemia was significantly higher in the enalapril group (11.3% vs 7.9% with placebo). The effect of ACE inhibitors on hematocrit may be mediated by N-AcetylSeryl-Aspartyl-Proline (Ac-SDKP) (goralatide), a tetrapeptide that inhibits erythropoiesis. As Ac-SDKP is metabolized by ACE, its accumulation in the presence of an ACE inhibitor may inhibit erythropoiesis and contribute to the observed anemia. Undoubtedly, HFrEF patients with ID should receive iron supplementation, as numerous trials4 have demonstrated its *Address correspondence. Dr Chia Siang Kow, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa, Bukit Jalil, Kuala Lumpur, Malaysia. [E-mail address: chiasiang_93@hotmail.com](E-mail address: chiasiang_93@hotmail.com) (C.S. Kow). Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2023) 86: 945. Received August 01, 2023; accepted August 2, 2023. doi: 10. 1097/JCMA.0000000000000984 Copyright © 2023, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/](http://creativecommons.org/licenses/)[ ](http://creativecommons.org/licenses/)[by-nc-nd/4.0/](by-nc-nd/4.0/)) beneficial effects in such cases. Nonetheless, it may be prudent to further explore the possibility of routine iron supplementationin all Chinese HFrEF patients who are receiving ACE inhibitors (not all patients may have access to sacubitril/valsartan due to cost considerations). Interestingly, dry cough has been reported in a significant proportion of patients treated with ACE inhibitors, and observations in

FAQs

How common is iron deficiency among HFrEF patients in the cited study?

Among the included HFrEF patients, 43.6% were found to have iron deficiency, regardless of anemia status.

Why do the authors discuss ACE inhibitors in relation to iron status?

The letter notes that renin-angiotensin system inhibitors—particularly ACE inhibitors—are associated with a higher incidence of anemia and may influence hematocrit. The discussion also extends to ACE-inhibitor–associated cough.

What treatment approach does the letter recommend for Chinese HFrEF patients on ACE inhibitors?

It suggests exploring routine iron supplementation to provide dual benefits: addressing iron deficiency and potentially mitigating ACE inhibitor–induced cough.

Sep 29, 2026

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