ACE Inhibitor Takers Plagued With Cough May Have Iron-Clad Cure

“Dry cough is the most often reported and troublesome complication associated with angiotensin-converting enzyme (ACE) inhibitor use, but its mechanism remains to be clarified,” says study author Kyung Pyo Hong, M.D. “Iron may be a key element in the control of the dry cough.”

ACE inhibitors are widely prescribed for the treatment of hypertension, heart failure and other cardiac conditions. They improve overall survival rates and reduce complications in patients with cardiovascular disease. While dry cough is not a serious complication, it is the most frequent reason people stop taking these medicines, says Hong, professor of medicine and chief, division of cardiology, Samsung Medical Center, Sungkyunkwan University, School of Medicine in Seoul, Korea.

According to the study, the incidence of ACE inhibitor-induced cough varies in published reports from 5 percent to 39 percent. This is the first study to look at the effect of iron on the cough caused by taking ACE inhibitors.

Small doses of iron may be enough to suppress the cough, Hong says.

Hong and his colleagues studied 19 Korean patients who had developed persistent dry cough while taking ACE inhibitors. The six men and 13 women were 60 years old on average. The researchers defined an ACE inhibitor-induced cough as a “dry cough that occurred during ACE inhibitor use and subsided within seven days after discontinuation of the drug and reappeared in 48 hours after reintroduction of the drug.” Participants completed a diary during an initial two-week observation period while taking the ACE inhibitor only. They were asked to score their cough severity on the following scale: 0: no cough; 1: a tickling sensation in the throat; 2: mild cough which did not interfere with daily activities; 3: moderate cough which was tolerable but severe enough to interrupt activities for some time; and 4: severe cough which persisted, interfered with daily activities and disturbed sleep at night. They recorded their cough scores for two 12-hour periods each day – between 8 a.m. and 8 p.m., then at night from 8 p.m. to 8 a.m. At the end of the observation period, researchers sampled participants’ blood and measured iron levels using various markers such as hemoglobin, hematocrit, serum iron concentration, ferritin levels, and total iron binding capacity (TIBC). Participants then took either a daily morning tablet of 256 milligrams ferrous sulfate (iron) or placebo for four weeks. Study subjects documented their coughs during the treatment period then gave another blood sample at the end of the four weeks.

The average daily cough score in the iron group was 3.07 at the end of the first two weeks, but 1.69 after four weeks of iron supplementation. Those in the placebo group did not have a significant change in their cough scores – 2.57 before and 2.35 after treatment. Eight of the 10 subjects in the iron group showed improvement in cough scores; whereas one in nine subjects in the placebo group showed improvement. Three patients in the iron group showed a near complete end to their coughing with a cough score of less than 1.

There was no significant difference in blood levels of hemoglobin, hematocrit, iron, TIBC or ferritin between the iron and placebo groups at the beginning of the study. Average ferritin levels increased in the iron group from 68.15 micrograms per liter (ug/L) at baseline to 86.03 ug/L after two weeks of iron treatment, but this difference did not reach a statistically significant level. Ferritin levels remained about the same in the placebo group (102.47 before and 98.97 after). There were no significant changes in hemoglobin, hematocrit, iron, or TIBC levels in either group.

“Supplementation of iron clearly showed a beneficial effect in most of these subjects, and this effect could not be found in the placebo group,” says Hong.

Iron supplementation has been reported to decrease the production of nitric oxide, which is known to have inflammatory effects on bronchial cells in the lungs.

Hong says that further investigation is warranted to verify these findings and study the long-term effects of iron supplementation with ACE inhibitors.

Other authors of the study include lead author Sang-Chol Lee, M.D.; Seung Woo Park, M.D.; Duk-Kyung Kim, M.D.; and Sang Hoon Lee, M.D.