From the Journals

Calcium channel blocker reduces cardiac iron loading in thalassemia major

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Targeting iron’s pathway into the heart

Why is this small clinical trial of such pivotal importance in this day and age of massive multicenter prospective randomized studies? The answer is that it tells us that iron entry into the heart through L-type calcium channels, a mechanism that has been clearly demonstrated in vitro, seems to be actually occurring in humans. As an added bonus, we have a possible new adjunctive treatment of iron cardiomyopathy. More clinical studies are needed, and certainly biochemical studies need to continue because all calcium channel blockers do not have the same effect in vitro, but at least the “channels” for more progress on both clinical and biochemical fronts are now open.

Thomas D. Coates, MD, is with Children’s Hospital of Los Angeles and University of Southern California, Los Angeles. He made his remarks in an editorial that accompanied the published study.



The calcium channel blocker amlodipine, added to iron chelation therapy, significantly reduced excess myocardial iron concentration in patients with thalassemia major, compared with chelation alone, according to results from a randomized trial.

The findings (Blood. 2016;128[12]:1555-61) suggest that amlodipine, a cheap, widely available drug with a well-established safety profile, may serve as an adjunct to standard treatment for people with thalassemia major and cardiac siderosis. Cardiovascular disease caused by excess myocardial iron remains a major cause of morbidity and mortality in thalassemia major.

Juliano L. Fernandes, MD, PhD, of the Jose Michel Kalaf Research Institute in Campinas, Brazil, led the study, which randomized 62 patients already receiving chelation treatment for thalassemia major to 1 year of chelation plus placebo (n = 31) or chelation plus 5 mg daily amlodipine (n = 31).

Patients in each arm were subdivided into two subgroups: those whose baseline myocardial iron concentration was within normal thresholds, and those with excess myocardial iron concentration as measured by magnetic resonance imaging (above 0.59 mg/g dry weight or with a cardiac T2* below 35 milliseconds).

In the amlodipine arm, patients with excess cardiac iron at baseline (n = 15) saw significant reductions in myocardial iron concentrations at 1 year, compared with those randomized to placebo (n = 15). The former had a median reduction of –0.26 mg/g (95% confidence interval, –1.02 to –0.01) while the placebo group saw an increase of 0.01 mg/g (95% CI, 20.13 to 20.23; P = .02).

The investigators acknowledged that some of the findings were limited by the study’s short observation period.

Patients without excess myocardial iron concentration at baseline did not see significant changes associated with amlodipine. While Dr. Fernandes and his colleagues could not conclude that the drug prevented excess cardiac iron from accumulating, “our data cannot rule out the possibility that extended use of amlodipine might prevent myocardial iron accumulation with a longer observation period.”

Secondary endpoints of the study included measurements of iron storage in the liver and of serum ferritin, neither of which appeared to be affected by amlodipine treatment, which the investigators said was consistent with the drug’s known mechanism of action. No serious adverse effects were reported related to amlodipine treatment.

Dr. Fernandes and his colleagues also did not find improvements in left ventricular ejection fraction associated with amlodipine use at 12 months. This may be due, they wrote in their analysis, to a “relatively low prevalence of reduced ejection fraction or severe myocardial siderosis upon trial enrollment, limiting the power of the study to assess these outcomes.”

The government of Brazil and the Sultan Bin Khalifa Translational Research Scholarship sponsored the study. Dr. Fernandes reported receiving fees from Novartis and Sanofi. The remaining 12 authors disclosed no conflicts of interest.

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