Context: Accumulation of iron in excess of physiologic requirements has been implicated in risk of cardiovascular disease because of increased iron-catalyzed free radical-mediated oxidative stress.
Objective: To test the hypothesis that reducing body iron stores through phlebotomy will influence clinical outcomes in a cohort of patients with symptomatic peripheral arterial disease (PAD).
Design, setting, and patients: Multicenter, randomized, controlled, single-blinded clinical trial based on the Iron (Fe) and Atherosclerosis Study (FeAST) (VA Cooperative Study #410) and conducted between May 1, 1999, and April 30, 2005, within the Department of Veterans Affairs Cooperative Studies Program and enrolling 1277 patients with symptomatic but stable PAD. Those with conditions likely to cause acute-phase increase of the ferritin level or with a diagnosis of visceral malignancy within the preceding 5 years were excluded. Analysis was by intent-to-treat.
Intervention: Patients were assigned to a control group (n = 641) or to a group undergoing reduction of iron stores by phlebotomy with removal of defined volumes of blood at 6-month intervals (avoiding iron deficiency) (n = 636), stratified by hospital, age, and baseline smoking status, diagnosis of diabetes mellitus, ratio of high-density to low-density lipoprotein cholesterol level, and ferritin level.
Main outcome measures: The primary end point was all-cause mortality; the secondary end point was death plus nonfatal myocardial infarction and stroke.
Results: There were no significant differences between treatment groups for the primary or secondary study end points. All-cause deaths occurred in 148 patients (23%) in the control group and in 125 (20%) in the iron-reduction group (hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.67-1.08; P = .17). Death plus nonfatal myocardial infarction and stroke occurred in 205 patients (32%) in the control group and in 180 (28%) in the iron-reduction group (HR, 0.88; 95% CI, 0.72-1.07; P = .20).
Conclusion: Reduction of body iron stores in patients with symptomatic PAD did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke.
Trial registration: Clinicaltrials.gov Identifier: NCT00032357.