A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major.

Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n = 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, -0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199.

The Blood Bank for Diabetes Screening: a Feasible Alternative?

BACKGROUND: Vascular complications of diabetes mellitus (DM) are associated with 5% of deaths globally every year. Early diagnosis and treatment could reduce this figure. The aim of this project was to investigate the frequency of undiagnosed DM among blood donors and the possibility of blood banks participating in DM screening. METHODS: Of the approximate 5,600 candidates for blood donation who were evaluated, 4,601 were considered suitable. Candidates with any type of DM, hypertension, thyroid disease, and/or continuous use of any drugs were excluded, resulting in the participation of 635 donors aged 18 - 69 years. Glycated hemoglobin (HbA1c) levels were used to classify the donors: HbA1c < 5.7% (low risk of DM), HbA1c 5.7 - 6.4% (pre-diabetes), and HbA1c ≥ 6.5% (diabetes). Another subsample (n = 576) that excluded donors with HbA1c levels < 5.0% or > 6.5% were classified according to the risk of developing DM in 5 years: HbA1c 5 - 5.5% (low risk, < 9%), HbA1c 5.6 - 6.0% (moderate risk, 9 - 25%), and HbA1c 6.1 - 6.5% (high risk, 26 - 50%). RESULTS: Three donors (0.5%) had HbA1c levels suggestive of DM, and 57 donors (9.0%) had levels associated with pre-DM. Regarding the risk of developing DM in 5 years, 111 donors (19.3%) were classified at moderate risk, and 10 donors (1.7%) were classified at high risk. CONCLUSIONS: DM screening in blood banks using HbA1c can identify new cases of DM and individuals at an increased risk of DM. In summary, blood banks could participate in DM screening, benefitting the general public and public health care system in Brazil.