Reducing iron stores does not benefit patients with peripheral arterial disease

Clinical Question

Does reducing iron stores improve outcomes for patients with symptomatic peripheral arterial disease?

Bottom Line

Reducing body iron stores by regular phlebotomy does not reduce the risk of adverse events for patients with symptomatic peripheral arterial disease (PAD). It remains possible, however, that a positive benefit may be seen with longer follow-up than 3.5 years, especially for individuals beginning treatment at a younger age (the mean age was 67 years in this study). (LOE = 1b)


Zacharski LR, Chow BK, Howes PS, et al. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease. A randomized controlled trial. JAMA 2007;297:603-610.  [PMID:17299195]

Study Design

Randomized controlled trial (single-blinded)






Outpatient (specialty)


Excessive accumulation of iron may increase the risk of cardiovascular disease. These investigators enrolled 1277 patients (mean age = 67 years), 99% of whom were men, with symptomatic PAD and an ankle-brachial blood pressure ratio of 0.85 or less. Subjects were required to have a hematocrit level of greater than 35% and a ferritin level of less than 400 ng/mL. Patients randomly received (concealed allocation assignment) phlebotomy at 6-month intervals (iron-reduction group) or usual care. Iron-reduction targeted a trough ferritin level of 25 ng/mL and a peak ferritin level prior to the next phlebotomy of 60 ng/mL. Complete follow-up occurred for 94% of patients for 3.5 years. Individuals assessing outcomes by patient review and medical record review remained blinded to treatment group assignment. Using intention-to-treat analysis, no significant differences were found between the groups for all-cause mortality, nonfatal myocardial infarction, and stroke. The study was 85% powered to detect 5% difference in outcomes.