Pediatric Clinics of North America - CIPERJ

ORAL IRON CHELATORS
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needed to determine the long-term safety and efficacy of doses greater
than 75 mg/kg per day.
Cardiac iron removal
A growing body of evidence supports the theory that deferiprone may
be more effective than deferoxamine at removing iron from the heart and
reducing iron-related cardiotoxicity [66,69–71]. In one retrospective study,
cardiac T2* and cardiac function were compared between 15 patients
who had thalassemia and were receiving long-term deferiprone and 30
matched controls receiving long-term deferoxamine [69]. Patients receiving
deferiprone had significantly less cardiac iron (median T2* 34 ms versus
11.4 ms, P ¼ .02). Furthermore, T2* values less than 20 ms, a level associated
with excess cardiac iron, were found in only 27% of patients
receiving deferiprone compared with 67% of those receiving deferoxamine
(P ¼ .025), despite a significantly greater liver iron concentration in those
receiving deferiprone. Left ventricular ejection fraction also was significantly
higher in the deferiprone-treated group. Moreover, in a multicenter,
retrospective study of patients who had thalassemia major, the risk for
cardiac complications (cardiac failure or arrhythmia requiring drug treatment)
was compared between 359 subjects who received only deferoxamine
and 157 patients who received deferiprone [70]. Fifty-two
patients (14.5%) developed cardiac events, including 10 deaths from cardiac
causes, during therapy with deferoxamine whereas no patients developed
cardiac events during treatment with deferiprone or within 18
months of discontinuing therapy.
A few prospective trials have compared the effect of deferiprone to deferoxamine
on cardiac iron removal and cardiac function [57,66,72,73]. Two
studies comparing deferiprone (75 mg/kg per day) to deferoxamine
(50 mg/kg per day, 5–6 days per week) showed no significant difference in
the reduction in cardiac iron between treatment groups after 1 year of therapy
[57,72]. A third study using similar dosing, however, showed a significantly
greater reduction in cardiac iron and improvement in left
ventricular ejection fraction with deferiprone than with deferoxamine after
3 years of therapy [73].
More recently, a multicenter, randomized, controlled clinical trial compared
deferiprone (average dose 92 mg/kg per day) to deferoxamine (average
dose 35 mg/kg per day, 7 days a week) for the treatment of 61 patients who
had thalassemia major and abnormal cardiac T2* (!20 ms) [66]. Patients
who had severe cardiac iron loading, T2* values less than 8 ms, or left
ventricular ejection fraction less than 56% were excluded. A significantly
greater improvement in T2* values was seen with deferiprone compared
with deferoxamine after 1 year of treatment (27% versus 13%, P ¼ .023).
Similarly, left ventricular ejection fraction increased more in those treated
with deferiprone (3.1% versus 0.3%, P ¼ .003).