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(Hypertension. 2001;38:166.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Iron Supplementation Inhibits Cough Associated With ACE Inhibitors

Sang-Chol Lee; Seung Woo Park; Duk-Kyung Kim; Sang Hoon Lee; Kyung Pyo Hong

From the Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Correspondence to Kyung Pyo Hong, MD, Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul, Korea 135-710. E-mail kphong{at}med.skku.ac.kr

Abstract—— Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07±0.70 and 1.69±1.10, respectively, for the iron group and 2.57±0.80 and 2.35±1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.

Key Words: angiotensin-converting enzyme inhibitors • cough • iron

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