BACKGROUND: Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored. METHODS: Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes. RESULTS: Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reduction patients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reduction patients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067). CONCLUSIONS: Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke. Published by Mosby, Inc.
RCT Entities:
BACKGROUND: Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored. METHODS: Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes. RESULTS:Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reductionpatients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reductionpatients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067). CONCLUSIONS: Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke. Published by Mosby, Inc.
Authors: Inês G Mollet; Dilipkumar Patel; Fatima S Govani; Adam Giess; Koralia Paschalaki; Manikandan Periyasamy; Elaine C Lidington; Justin C Mason; Michael D Jones; Laurence Game; Simak Ali; Claire L Shovlin Journal: PLoS One Date: 2016-02-11 Impact factor: 3.240