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 eval...

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Bibliographic Details
Published in:Blood 2016-09, Vol.128 (12), p.1555-1561
Main Authors: Fernandes, Juliano L., Loggetto, Sandra R., Veríssimo, Monica P.A., Fertrin, Kleber Y., Baldanzi, Giorgio R., Fioravante, Luciana A.B., Tan, Doralice M., Higa, Tatiana, Mashima, Denise A., Piga, Antonio, Coelho, Otavio R., Costa, Fernando F., Saad, Sara T.
Format: Article
Language:English
Subjects:
Administration, Oral
Adolescent
Adult
Amlodipine - therapeutic use
beta-Thalassemia - drug therapy
Chelation Therapy
Child
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Iron - metabolism
Male
Middle Aged
Myocardium - metabolism
Prognosis
Vasodilator Agents - therapeutic use
Young Adult
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Summary: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*
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2016-06-721183